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Dietary Supplement Fact Sheet: Vitamin D

pharmacist, or other qualified health professional about the appropriateness of taking dietary supplements and their potential
interactions with medications.
Offi ce of Dietary Supplements
National Insti tutes of Health
Bethesda. Maryland 20892 USA
Web: ht!D:I/ods ad njh goy
E mail : ods@nih.gov
Document Last Updated: 11/13/2009 2:37 PM
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Dietary Supplement Fact Sheet: Vitamin D
OFFICT OF
DII:.IARY
SUPPLE tENTS
Dietary Supplement Fact Sheet
Table of Contents
Introduction
Reference Intakes
Sources of Vitamin D
Vitamin D Intakes and Status
Vitamin D Deficiency
Groups at Risk of Vitamin D Inadequacy
Vitamin D and Health
Health Risks from Excessive Vitamin D
Interactions with Medications
Vitamin D and Healthful Diets
References
Introduction
Vitamin D
Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary
supplement. It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis
[1,2]. Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two hydroxylations in
the body for activation. The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D [25(0H)D], also known as
calcidiol. The second occurs primarily in the kidney and forms the physiologicall y active 1,25-dihydroxyvitamin D [1,25(0H}2D], also
known as calcitriol [3].
Vitamin D is essential for promoting calcium absorption in the gut and maintaining adequate serum calcium and phosphate
concentrations to enable normal mineralization of bone and prevent hypocalcemic tetany. It is also needed for bone growth and
bone remodeling by osteoblasts and osteoclasts [3,4,5] . Without sufficient vitamin D, bones can become thin, brittle, or misshapen.
Vitamin D sufficiency prevents rickets in children and osteomalacia in adults [2,6, 7] . Together with calcium, vitamin D also helps
protect older adults from osteoporosis.
Vitamin D has other roles in human health, including modulation of neuromuscular and immune function and reduction of
inflammation. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by
vitamin D [3,5,8,9] . Many laboratory-cultured human cells have vitamin D receptors and some convert 25(0H)D to 1,25(0H}zD [10] .
It remains to be determined whether cells with vitamin D receptors in the intact human carry out this conversion.
Serum concentration of 25(0H)D is the best indicator of vitamin D status. It reflects vitamin D produced cutaneously and that
obtained from food and supplements [4] and has a fairly long circulating half-life of 15 days [11 ]. However, serum 25(0H)D levels do
not indicate the amount of vi tamin D stored in other body tissues. Circulating 1,25(0H}zD is generally not a good indicator of
vitamin D status because it has a short half -life of 15 hours and serum concentrations are closely regulated by parathyroid hormone,
calcium, and phosphate [ 11]. Levels of 1,25(0H}zD do not typically decrease until vitamin D deficiency is severe [ 5, 10].
There is considerable discussion of the serum concentrations of 25(0H)D associated with deficiency (e.g. , rickets), adequacy for
bone health, and optimal overall health (Table 1 ). A concentration of <15 nanograms per milliliter (ng/ml) (or <37 .5 nanomoles per
liter [nmoi/L]) is generally considered inadequate; concentrations >15 ng/ml (>37 . 5 nmoi/L) are recommended. Higher levels are
proposed by some (>30 ng/ml or >75 nmoi/L) as desirable for overall health and disease prevention [12], but insufficient data are
available to support them [ 13]. Serum concentrations of 25(0H)D consistently >200 ng/ml (>500 nmoi/L) are potentially toxic.
Ta bl d e 1: Serum 25-Hyc roxyvitamin D [25(0H}D] Concentrations an d I h* Heat
I ngtmL ** II nmoltL ** II
Health status
1<10-11 11<25-27.5
with vitamin D deficiency, leading to rickets in infants and children and osteomalacia in
adults [ 4, 13]
1<10-15 11<25-37. 5 !I Generally considered inadequate for bone and overall health in healthy individual s [4,13]
1=15 11 =37.5 !IGenerally considered adequate for bone and overall health in healthy individuals [4]
II II II
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Dietary Supplement Fact Sheet: Vitamin D
Consistently Consistently Considered potentially toxic, leading to hypercalcemia and hyperphosphatemia, although human data
>200 >500 are limited. In an ani mal model, concentrations =400 ng/ml (=1,000 nmoi/L) demonstrated no toxicity
[11,14].
. . .
*Serum concentrations of 25(0H)D are reported m both nanograms per millil iter (ng/ml) and nanomoles per liter (nmoi/L) .
** 1 ng/ml = 2.5 nmoi/L
An additional compl ication in assessing vitamin D status is in the actual measurement of serum concentrations of 25(0H)D.
Considerable variability exists among the various assays available and among laboratories that conduct the analyses [15, 16, 17]. This
means that compared to the actual concentration of 25(0H)D in a sample of blood serum, a falsely low or falsely high value may be
obtained depending on the assay or laboratory used [18]. A standard reference material for 25(0H)D became avail abl e in july 2009
that will now permit standardization of values across laboratories [19].
Reference Intakes
Intake reference values for vi t amin D and other nutrients are provided in the Dietary Reference Intakes (ORis) developed by the
Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies (formerly National Academy of Sciences) [4].
DRI is the general term for a set of reference val ues used to plan and assess nutrient intakes of healthy people. These val ues, which
vary by age and gender [4], include:
Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly
all (97%-98%) healthy people.
Adequate Int ake (AI): establi shed when evidence is insufficient t o develop an RDA and is set at a level assumed to ensure
nutritional adequacy.
Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects [4].
The FNB established an AI for vitami n D that represents a dail y intake that is sufficient to maintain bone health and normal calcium
metabolism i n healthy people. Ais for vitami n D are listed in both micrograms (meg) and International Units (IUs); the biological
activity of 1 meg is equal to 40 IU (Table 2). The Ais for vitamin D are based on the assumption that the vitamin is not synthesized
by exposure to sunl ight [4].
bl d k Ta e 2: A equate Inta es (Als) or VItamin D [ 4]
I
Age IIChildrenll Men IIWomeniiPregnancyiiLactationl
meg
B1rth to 13 years (
200
IU)
ID O l II I
114-18 years
5 meg 5 meg ,,,5 meg
(200 IU) (200 IU) (200 IU)

(200 IU)
119-50 years
5 meg 5 meg

(200 IU) (200 IU) (200 IU) (200 IU)
151-70 years

10 meg 10 meg
I II I
(400 IU) (400 IU)
171+ years

15 meg 15 meg
I II I
(600 IU) (600 IU)
In 2008, the American Academy of Pediatrics (MP) issued recommended intakes for vitamin D that exceed those of FNB [20]. The
AAP recommendat ions are based on evidence from more recent cl inical trials and the history of safe use of 400 IU/day of vitamin D
in pediatric and adolescent populations. MP recommends that exclusively and partially breastfed infants receive supplements of
400 IU/day of vitamin D shortly after birth and continue to receive these supplements until they are weaned and consume =1 ,000
mllday of vitamin D-fortified formula or whole milk [20]. (All formulas sold in the Uni t ed States provide =400 IU vitamin 0
3
per
liter, and the majority of vitamin D-only and multivitamin liquid supplements provide 400 IU per serving.) Simil arly, all non-
breastfed infants i ngesting <1 ,000 mllday of vitamin D-fortified formula or milk should receive a vitamin D suppl ement of 400
IU/day. MP also recommends that older children and adolescents who do not obtain 400 IU/day through vitamin D-fortified milk
and foods should take a 400 IU vitamin D supplement dai ly [20].
The FNB established an expert committee in 2008 to review the ORis for vitamin D (and calcium). The current DR!s for this nutri ent
were established in 1997, and since t hat time substantial new research has been published to justify a reevaluation of adequate
vitamin D intakes for healthy populations. Determinations of ORis are based on i ndicators of adequacy or hazard; dose-response
curves; health outcomes; life-stage groups; and relations between intakes, biomarkers, and outcomes. For vitamin D, the FNB
committee will focus on (1) effects of circulating concentrations of 25(0H)D on health outcomes, (2) effects of vitamin D intakes on
circulating 25(0H)D and on health outcomes, and (3) levels of intake associated with adverse effects [21]. The FNB expects to issue
its report, updat ing as appropriate the ORis for vitamin D and calcium, by May 2010 [22].
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Dietary Supplement Fact Sheet: Vitamin D
Sources of Vitamin D
Food
Very few foods in nature contain vitamin D. The flesh of fish (such as salmon, tuna, and mackerel) and fish liver oils are among the
best sources [4]. Small amounts of vitamin Dare found in beef liver, cheese, and egg yolks. Vitamin Din these foods is primarily in
the form of vitamin D3 (cholecalciferol) and its metabolite 25(0H)D3 [23]. Some mushrooms provide vitamin D2 (ergocalciferol) in
variable amounts [24-26]. Mushrooms with enhanced l evels of vitamin D
2
from being exposed to ultraviolet light under controlled
conditions are also avail able.
Fortified foods provide most of the vitamin Din the American diet [4,26]. For example, almost all of the U.S. milk supply is fortified
with 100 IU/cup of vitamin D (25% of the Dai ly Value or 50% of the AI level for ages 14-50 years). In the 1930s, a mi l k fortification
program was implemented in the United States to combat rickets, then a major public health problem. This program virtually
eliminated the disorder at that time [4, 14]. Other dairy products made from milk, such as cheese and ice cream, are generally not
fortified. Ready-to-eat breakfast cereals often contain added vitamin D, as do some brands of orange juice, yogurt, and margarine.
In the United States, foods all owed to be fortified with vitamin D include cereal flours and related products, milk and products
made from milk, and calcium-fortified fruit juices and drinks [27]. Maximum levels of added vitamin Dare specified by law.
Several food sources of vitamin D are listed in Table 3.
Table 3 Selected Food Sources of Vitamin D [ 30) .
I
Food
IUs per
serving*
II Percent
DV**
lcod liver oil, 1 tablespoon 1,360 340
!salmon (sockeye), cooked, 3 ounces 794 199
Mushrooms that have been exposed to ultraviolet light to increase vitamin D, 3 ounces (not yet
400 100
commonly available)
!Mackerel, cooked, 3 ounces 388 97
!Tuna f ish, canned in water, drained, 3 ounces 154 39
IMilk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup 115-124 29-31
Orange juice fortified with vitamin D, 1 cup (check product labels, as amount of added vitamin D
100 25
varies)
Yogurt, fortified with 20% of the DV for vitamin D, 6 ounces (more heavily fortified yogurts provide
80 20
more of the DV)
!Margarine, fortified, 1 tablespoon 60 15
!sardines, canned in oil, drained, 2 sardines 46 12
!Liver, beef, cooked, 3.5 ounces 46 12
Ready-to-eat cereal , fortified with 10% of the DV for vitamin D, 0.75-1 cup (more heavily fortified
40 10
cereals might provide more of the DV)
IEgg, 1 whole (vitamin D is found in yolk) 25 6
!cheese, Swiss, 1 ounce 6 2
*IUs = International Units.
**DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration to help consumers compare t he nutrient
contents of products within the context of a total diet. The DV for vitamin D is 400 IU for adults and chi ldren age 4 and older.
Food labels, however, are not required to list vitamin D content unless a food has been fortified with this nutrient. Foods
providing 20% or more of the DV are considered to be high sources of a nutrient.
The U.S. Department of Agriculture's Nutrient Database Web site, http://www.nal.usda.gov/fnic/foodcomp/search, lists the
nutrient content of many foods and provides a list of foods containing vitamin D:
http;//www.ars.usda.gov/SP2UserFiles/Piace/123545QO/Data/SR22/nutrlist/sr22a324,pdf . A growing number of foods are bei ng
analyzed for vitamin D content. Simpler and faster methods to measure vitamin D in foods are needed, as are food standard
reference materials with certified values for vitamin D to ensure accurate measurements [31 ].
Sun exposure
Most people meet their vitamin D needs through exposure to sunlight [5,31]. Ultraviolet (UV) B radiation with a wavelength of 290-
315 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D
3
, which in turn becomes
vitamin D
3
[9,32,33]. Season, geographic latitude, time of day, cloud cover, smog, skin melanin content, and sunscreen are among
the factors that affect UV radiation exposure and vitamin D synthesis [33]. The UV energy above 42 degrees north latitude (a l ine
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approximately between the northern border of California and Boston) is insufficient for cutaneous vitamin D synthesis from
November through February [5]; in far northern latitudes, this reduced intensity lasts for up to 6 months. In the United States,
latitudes below 34 degrees north (a line between Los Angeles and Columbia, South Carolina) allow for cutaneous production of
vitamin D throughout the year [27].
Complete cloud cover reduces UV energy by 50%; shade (including that produced by severe pollution) reduces it by 60% [34]. UVB
radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce vitamin D [35]. Sunscreens
with a sun protection factor of 8 or more appear to block vitamin D-producing UV rays, although in practice people generally do not
apply sufficient amounts, cover all sun-exposed skin, or reapply sunscreen regularly [36]. Skin likely synthesizes some vitamin D
even when it is protected by sunscreen as typically applied.
The factors that affect UV radiation exposure and research to date on the amount of sun exposure needed to maintain adequate
vitamin D levels make it difficult to provide general guidelines. It has been suggested by some vitamin D researchers, for example,
that approximately 5-30 minutes of sun exposure between 10 AM and 3 PM at least twice a week to the face, arms, legs, or back
without sunscreen usually lead to sufficient vitamin D synthesis and that the moderate use of commercial t anning beds that emit
2%-6% UVB radiation is also effective [10,33]. Individuals with limited sun exposure need to include good sources of vitamin Din
thei r diet or take a supplement.
Despite the importance of the sun to vitamin D synthesis, it is prudent to limit exposure of skin to sunlight [36] and UV radiation
from tanning beds [37]. UV radiation is a carcinogen responsible for most of the estimated 1.5 million skin cancers and the 8,000
deaths due to metastatic melanoma that occur annually in the United States [36]. Lifetime cumulative UV damage to skin is also
largely responsible for some age-associated dryness and other cosmetic changes. It is not known whether a desirable level of regular
sun exposure exists that imposes no (or minimal) risk of skin cancer over time. The American Academy of Dermatology advises that
photoprotective measures be taken, including the use of sunscreen, whenever one is exposed to the sun [38].
Dietary supplements
In supplements and fortified foods, vitamin D is available in two forms, 0
2
(ergocalciferol) and 0
3
(cholecalciferol). Vitamin 0
2
is
manufactured by the UV irradiation of ergosterol in yeast, and vitamin D3 is manufactured by the irradiation of 7-dehydrocholesterol
from lanolin and the chemical conversion of cholesterol [ 10]. The t wo forms have t raditionally been regarded as equivalent based
on their ability to cure rickets, but evidence has been offered that they are metabolized differently. Vitamin 0
3
could be more than
three times as effective as vitamin 0
2
in raising serum 25(0H)D concentrations and maintaining those levels for a longer time, and
its metabolites have superior affinity for vitamin D-binding proteins in plasma [5,39,40]. Because metabolite receptor affinity is not
a functional assessment, as the earlier results for the healing of rickets were, further research is needed on the comparative
physiological effects of both forms. Many supplements are being reformulated to contain vitamin 0
3
instead of vitamin 0
2
[40]. Both
forms (as well as vitamin D in foods and from cutaneous synthesis) effectively raise serum 25(0H)D levels [5].
Vitamin D Intakes and Status
In 1988-1994, as part of the thi rd National Health and Nutrition Examination Survey (NHANES III), the frequency of use of some
vitamin D-containing foods and supplements was examined in 1,546 non-Hispanic African American women and 1,426 non-Hispanic
white women of reproductive age (15-49 years) [41 ]. In both groups, 25(0H)D levels were higher in the fall (after a summer of sun
exposure) and when milk or fortified cereals were consumed more than three times per week. The prevalence of serum
concentrations of 25(0H)D =15 ng/ml (=37 .5 nmoi/L) was 10 times greater for the African American women (42.2%) than for the
white women (4.2%).
The 2000-2004 NHANES provides the most recent data on the vitamin D nutritional status of the U.S. population. Generally, younger
people had higher serum 25(0H)D levels t han older people, males had higher levels than females, and non- Hispanic whites had
higher levels than Mexican Americans, who in turn had higher level s than non-Hispanic blacks. Depending on the population group,
1%-9% had serum 25(0H)D levels <11 ng/ml (<27.5 nmoi/L), 8%-36% had levels <20 ng/ml (<50 nmoi/L), and t he majority (50%-78%)
had levels <30 ng/ml (<75 nmoi/L) [42].
In NHANES 2000-2004, age-adjusted mean serum 25(0H)D concentrations were 2-8 ng/ml (5-20 nmoi/L) lower compared to NHANES
III [ 43]. However, after adjustment for assay shifts, age-adjusted means in NHANES 2000-2004 remained significantly lower (by 2.0-
3.6 ng/ml (5-9 nmoi/L)) in most males, but not in most females. In a study subsample, adjustment for the confounding effects of
assay differences changed mean serum 25(0H)D concentrations by - 4 ng/ml (-10 nmoi/L), and adjustment for changes in the
factors likely related to real changes in vitamin D status (such as body mass index (BMI), milk intake, and sun protection) changed
mean serum 25(0H)D concentrations by 0.4-0.64 ng/ml (1.0-1.6 nmoi/L).
Subsequent to this report, another investigator [44] evaluated vitamin D levels measured in NHANES 2001-2004 compared to NHANES
III and reported a marked decline, leading some to suggest that the majority of children and adults in the United States (and almost
all African Americans and Mexican Americans) are vitamin D insufficient. However, this analysis exaggerates the temporal and
demographic trends in vitamin D status because it uses a higher than usual cutoff to characterize vitamin D insufficiency, does not
separate the independent effects of season and latitude in data and, most seriously, fails to compensate for a change in the
25(0H)D measurement assay used between both sets of NHANES surveys [45]. Over time, mean serum 25(0H)D concentrations in the
United States have declined, but only modestly, when compensating for the assay change [43]. The real decline (-2.0-3.6 ng/ml
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Dietary Supplement Fact Sheet: Vitamin D
(-S-9 nmoi/L)) is likely due to simultaneous increases in BMI, reduced milk intake, and greater use of sun protection in the U.S.
population.
According to NHANES data from 2005-2006, only 29% of adult men and 17% of adult women (ages 19 and older) had intakes of
vitamin D from food alone that exceeded their Ais. Overall in the U.S. population, only about one-third of individuals 1 year of age
and older had vitamin D intakes from food exceeding their respective Ais [46]. However, dietary supplements as well as foods
contribute vitamin D, so both sources must be included to obtain a true picture of total intakes. In 2005-2006, 37% of people in the
United States reported the use of a dietary supplement containing vitamin D. Total intake estimates of vitamin D from both food and
supplements are currently being tabulated by the Office of Dietary Supplements.
Vitamin D Deficiency
Nutrient deficiencies are usually the result of dietary inadequacy, impaired absorption and use, increased requirement, or increased
excretion. A vitamin D deficiency can occur when usual intake is lower than recommended levels over time, exposure to sunlight is
limited, the kidneys cannot convert vitamin D to its active form, or absorption of vitamin D from the digestive tract is inadequate.
Vitamin D-deficient diets are associated with milk allergy, lactose intolerance, and strict vegetarianism [47].
Rickets and osteomalacia are the classical vitamin D deficiency diseases. In children, vitamin D deficiency causes rickets, a disease
characterized by a failure of bone tissue to properly mineralize, resulting in soft bones and skeletal deformities [34]. Rickets was
first described in the mid-17th century by British researchers [34,48]. In the late 19th and early 20th centuries, German physicians
noted that consuming 1-3 teaspoons of cod liver oil per day could reverse rickets [48]. In the 1920s and prior to identification of
the structure of vitamin D and its metabolites, biochemist Harry Steenbock patented a process to impart antirachitic activity to
foods [27]. The process involved the addition of what turned out to be precursor forms of vitamin D followed by exposure to UV
radiation. The fortification of milk with vitamin D has made rickets a rare disease in the United States. However, rickets is still
reported periodically, particularly among African American infants and children [34,48]. A 2003 report from Memphis, for example,
described 21 cases of rickets among infants, 20 of whom were African American [48].
Prolonged exclusive breastfeeding without the AAP-recommended vitamin D supplementation is a significant cause of rickets,
particularly in dark-skinned infants breastfed by mothers who are not vitamin D replete [6]. Additional causes of rickets include
extensive use of sunscreens and placement of children in daycare programs, where they often have less outdoor activity and sun
exposure [34,48]. Rickets is also more prevalent among immigrants from Asia, Africa, and the Middle East, possibly because of
genetic differences in vitamin D metabolism and behavioral differences that lead to less sun exposure [34].
In adults, vitamin D deficiency can lead to osteomalacia, resulting i n weak muscles and bones [6, 7,11 ]. Symptoms of bone pain and
muscle weakness can indicate inadequate vitamin D levels, but such symptoms can be subtle and go undetected in the initial stages.
Groups at Risk of Vitamin D Inadequacy
Obtaining sufficient vitamin D from natural food sources alone can be difficult. For many people, consuming vitamin D-fortified
foods and being exposed to sunlight are essential for maintaining a healthy vitamin D status. In some groups, dietary supplements
might be required to meet the daily need for vitamin D.
Breastfed infants
Vitamin D requirements cannot be met by human mi lk alone [4,49], which provides only about 25 IU/L [SO]. A recent review of
reports of nutritional ricket s found that a majority of cases occurred among young, breastfed African Americans [51]. The sun is a
potential source of vi tamin D, but AAP advises keeping infants out of direct sunlight and having them wear protective clothing and
sunscreen [52]. As noted earlier, MP recommends that exclusively and partially breastfed infants be supplemented with 400 IU of
vitamin D per day [20].
Older adults
Americans aged SO and older are at increased risk of developing vitamin D insufficiency [33]. As people age, skin cannot synthesize
vitamin D as efficiently and the kidney is less able to convert vitamin D to its active hormone form [4,53]. As many as half of older
adults in the United States with hip fractures could have serum 2S(OH)D levels <12 ng/ml (<30 nmoi/L) [5] .
People with limited sun exposure
Homebound individuals, people living in northern latitudes (such as New England and Alaska), women who wear long robes and head
coverings for religious reasons, and people with occupations that prevent sun exposure are unlikely to obtain adequate vitamin D
from sunlight [54,55].
People with dark skin
Greater amounts of the pigment melanin result in darker skin and reduce the skin's ability to produce vitamin D from exposure to
sunlight. Some studies suggest that older adults, especially women, with darker skin are at high risk of developing vitamin D
insufficiency [41 ,56]. However, one group with dark skin, African Americans, general ly has lower levels of 25(0H)D yet develops
fewer osteoporotic fractures than Caucasians (see section below on osteoporosis).
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Dietary Supplement Fact Sheet: Vitamin D
People with fat malabsorption
As a fat-soluble vitamin, vitamin D requires some dietary fat in the gut for absorption. Individuals who have a reduced ability to
absorb dietary fat might require vitamin 0 supplements [57]. Fat malabsorption is associated with a variety of medical conditions
including some forms of liver disease, cystic fibrosis, and Crohn's disease [27].
People who are obese or who have undergone gastric bypass surgery
Individuals with a BMI =30 typically have a low plasma concentration of 25(0H)D [58]; this level decreases as obesity and body fat
increase [59]. Obesity does not affect skin's capacity to synthesize vitamin D, but greater amounts of subcutaneous fat sequester
more of the vitamin and alter its release into the circulation. Even with orally administered vitamin D, BMI is inversely correlated
with peak serum concentrations, probably because some vitamin 0 is sequestered in the larger pools of body fat [58]. Obese
individuals who have undergone gastric bypass surgery may become vitamin D deficient without a sufficient intake of this nutrient
from food or supplements, since part of the upper small intestine where vitamin Dis absorbed is bypassed [60,61].
Vitamin D and Health
Optimal serum concentrations of 25(0H)D for bone and general health throughout life have not been established [5, 1 0] and are
likely to vary at each stage of life, depending on the physiological measures selected. The three-fold range of cut points that have
been proposed by various experts, from 16 to 48 ng/ml (40 to 120 nmoi/L), reflect differences in the functional endpoints chosen
(e.g., serum concentrations of parathyroid hormone or bone fractures), as well as differences in the analytical methods used.
In March 2007, a group of vitamin D and nutrition researchers published a controversial and provocative editorial contending that
the desirable concentration of 25(0H)D is =30 ng/ml {=75 nmoi/L) [12]. They noted that supplemental intakes of 400 IU/day of
vitamin D increase 25(0H)D concentrations by only 2.8-4.8 ng/mL (7-12 nmoi/L) and that daily intakes of approximately 1,700 IU
are needed to raise these concentrations from 20 to 32 ng/ml (50 to 80 nmoi/L).
Osteoporosis
More than 25 million adults in the United States have or are at risk of developing osteoporosis, a disease characterized by fragile
bones that significantly increases the risk of bone fractures [62]. Osteoporosis is most often associated with inadequate calcium
intakes (generally <1 ,000-1,200 mg/day}, but insufficient vitamin D contributes to osteoporosis by reducing calcium absorption [63].
Although rickets and osteomalacia are extreme examples of the effects of vitamin D deficiency, osteoporosis is an example of a
long-term effect of calcium and vitamin 0 insufficiency [64]. Adequate storage levels of vitamin D maintain bone strength and might
help prevent osteoporosis in older adults, nonambulatory individuals who have difficulty exercising, postmenopausal women, and
individuals on chronic steroid therapy [65].
Normal bone is constantly being remodeled. During menopause, the balance between these processes changes, resulting in more
bone being resorbed than rebuilt. Hormone therapy with estrogen and progesterone might be able to delay the onset of
osteoporosis. However, some medical groups and professional societies recommend that postmenopausal women consider using
other agents to slow or stop bone resorption because of the potential adverse health effects of hormone therapy [66-68].
Most supplementation trials of t he effects of vitamin D on bone health also include calcium, so it is not possible to isolate the
effects of each nutrient. The authors of a recent evidence-based review of research concluded that supplements of both vitamin D3
(at 700-800 IU/day) and calcium (500-1 ,200 mg/day) decreased the risk of falls, fractures, and bone loss in elderly individuals aged
62-85 years [5]. The decreased risk of fractures occurred primarily in elderly women aged 85 years, on average, and living in a
nursing home. Women should consult their healthcare providers about their needs for vitamin D (and calcium) as part of an overall
plan to prevent or t reat osteoporosis.
African Americans have lower levels of 25(0H)D than Caucasians, yet they develop fewer osteoporotic fractures. This suggests that
factors other than vitamin D provi de protection [69]. African Americans have an advantage in bone density from early childhood, a
function of their more efficient calcium economy, and have a lower risk of fracture even when they have the same bone density as
Caucasians. They also have a higher prevalence of obesity, and the resulting higher estrogen levels in obese women might protect
t hem from bone loss [69]. Further reducing the risk of osteoporosis in African Americans are their lower levels of bone-turnover
markers, shorter hip-axis length, and superior renal calcium conservation. However, despite this advantage in bone density,
osteoporosis is a signifi cant health problem among African Americans as they age [69].
Cancer
Laboratory and animal evidence as well as epidemiologic data suggest that vitamin 0 status could affect cancer risk. Strong
biological and mechanistic bases indicate that vitamin D plays a role in the prevention of colon, prostate, and breast cancers.
Emerging epidemiologic data suggest that vitamin D has a protective effect against colon cancer, but the data are not as strong for
a protective effect against prostate and breast cancer, and are variable for cancers at other sites [70, 71 ]. Studies do not
consistently show a protective effect or no effect, however. One study of Finnish smokers, for example, found that subjects in t he
highest quintile of baseline vitamin D status have a three-fold higher risk of developing pancreatic cancer [72].
Vitamin D emerged as a protective factor in a prospective, cross-sectional study of 3,121 adults aged =50 years (96% men) who
underwent a colonoscopy. The study found that 10% had at least one advanced cancerous lesion. Those with the highest vitamin D
intakes {>645 IU/day) had a significantly lower risk of these lesions [73]. However, the Women's Health Initiative, in which 36,282
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Dietary Supplement Fact Sheet: Vitamin D
postmenopausal women of various races and ethnicities were randomly assigned to receive 400 IU vitamin D plus 1,000 mg calcium
daily or a placebo, found no significant differences between the groups in the incidence of colorectal cancers over 7 years [74].
More recently, a clinical trial focused on bone health i n 1,179 postmenopausal women residing in rural Nebraska found that subj ects
supplemented daily with calcium (1 ,400-1,500 mg) and vitamin 0
3
(1, 100 IU) had a significantly lower incidence of cancer over 4
years compared to women taking a placebo [64] . The small number of cancers reported (50) precludes generalizing about a
protective effect from either or both nutrients or for cancers at different sites. This caution is supported by an analysis of 16,618
participants in NHANES III, where total cancer mortality was found to be unrelated to baseline vitamin D status [76]. However,
colorectal cancer mortality was inversely related to serum 25(0H)D concentrations.
Further research is needed to determine whether vitamin D inadequacy in particular increases cancer risk, whether greater exposure
to the nutrient is protective, and whether some individuals could be at increased risk of cancer because of vitamin D exposure
[70, 77] .
Other conditions
A growing body of research suggests that vitamin D might play some rol e in the prevention and treatment of type 1 [78] and type 2
diabetes [79]. hypertension [80]. glucose i ntolerance [81]. multiple sclerosis [82], and other medical conditions [83,84]. However,
most evidence for these rol es comes from i n vitro, ani mal, and epidemiol ogical studies, not the randomized cl i ni cal trials
considered to be more definitive. Unti l such trials are conducted, the implications of the avai labl e evidence for public health and
patient care will be debated. A systematic review of health outcomes related to vitamin D and calcium i ntakes, both alone and in
combination, was published in August 2009 [85].
A recent meta-analysis found that use of vitamin D supplements was associated with a reduction in overall mortality from any cause
by a statistically signifi cant 7% [86,87]. The subj ects in these trials were pri mari ly healthy, middl e aged or elderly, and at high risk
of fractures; they took 300-2,000 IU/day of vitamin D supplements.
Health Risks from Excessive Vitamin D
Vitamin D toxicity can cause nonspecific symptoms such as nausea, vomiting, poor appetite, constipation, weakness, and weight loss
[88]. More seriously, it can also raise blood levels of calci um, causing mental status changes such as confusion and heart rhythm
abnormali ties [7]. The use of supplements of both calcium (1 ,000 mg/day) and vitamin D (400 IU/day) by postmenopausal women
was associated with a 17% increase in the risk of kidney stones over 7 years in the Women's Health Initiative [89] . Deposition of
calcium and phosphate in the kidneys and other soft tissues can also be caused by excessive vitamin D levels [47]. A serum 25(0H)D
concentration consistently >200 ng/ml (>500 nmoi/L) is considered to be pot entially toxic [11 ] . In an animal model, concentrations
=400 ng/ml (=1,000 nmoi/L) were not associated with harm [ 14].
Excessive sun exposure does not result in vitamin D toxi city because the sust ained heat on the skin is thought to photodegrade
previtamin 0
3
and vitamin 0
3
as it is formed [10,35]. High intakes of dietary vitami n Dare very unlikely to result in toxicity unless
large amounts of cod liver oil are consumed; toxicity is more likely to occur from high intakes of supplements.
Long-term int akes above the UL increase the risk of adverse health effects [4] (Table 4). Substantially larger doses administered for
a short time or periodically (e.g., 50,000 IU/week for 8 weeks) do not cause toxicity. Rather, the excess is stored and used as
needed to maintain normal serum 25(0H)D concentrations when vitamin D intakes or sun exposure are limited [ 11, 90].
T bl 4 T I bl U a e : o era e 1pper nta e eve s or 1tamm k l I (Uls) f v
. D [4]
I
Age II Childrenll Men II Women IIPregnancyiiLactation I
Birth to 12 months
25 meg
CJCJI II I
(1 ,000 IU)
11-13 years
ISO meg
. (2,000 IU)
CJCJI II I
114+ years meg meg meg
. (2,000 IU) (2,000 IU) (2,000 IU)
meg
(2,000 IU)
Several nutrition scientists recently challenged these Uls, first published in 1997 [90]. They point to newer clinical trials conducted
in healthy adults and conclude that t he data support aULas high as 10,000 IU/day. Although vitamin D supplements above
recommended levels given in clinical trials have not shown harm, most trials were not adequately designed to assess harm [5].
Evidence is not sufficient to determine the potential risks of excess vitamin D in infants, children, and women of reproductive age.
As noted earlier, the FNB is current ly reviewi ng data to determine whether updates to the ORis (incl uding the Uls) for vitamin Dare
appropriate [4].
Interactions with Medications
Vitamin D suppl ements have the potential to interact with several types of medications. A few examples are provided below.
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Dietary Supplement Fact Sheet: Vitamin D
Individuals taking these medications on a regular basis should discuss vitamin D intakes with their healthcare providers.
Steroids
Corticosteroid medications such as prednisone, often prescri bed to reduce inflammation, can reduce calcium absorption [ 91-93] and
impair vitamin D metaboli sm. These effects can further contribut e t o the loss of bone and the development of osteoporosis
associated with their long-term use [ 92, 93].
Other medications
Both the weight-loss drug orli stat (brand names Xenical and aiiPM) and the cholesterol-lowering drug cholestyramine (brand names
Questran, LoCholest, and Prevalite) can reduce the absorption of vitamin D and other fat-soluble vitamins [ 94,95]. Both
phenobarbital and phenytoin (brand name Dilantin), used to prevent and control epi l eptic seizures, increase the hepatic
metabolism of vitamin D t o inactive compounds and reduce calcium absorption [96].
Vitamin D and Healthful Diets
According to the 2005 Dietary Guidelines for Americans, "nutrient needs should be met primarily through consuming foods. Foods
provide an array of nut rient s and other compounds that may have beneficial effects on health. I n cert ain cases, fortified foods and
dietary supplements may be useful sources of one or more nutrients that otherwise might be consumed i n less than recommended
amounts. However, dietary supplements, while recommended in some cases, cannot replace a healthful diet. "
The Dietary Guidelines for Americans describes a healthy di et as one that
Emphasizes a variety of fruits, vegetables, whole grains, and fat-free or low-fat milk and milk products.
Mil k is fortified with vitamin D, as are many ready-to-eat cereals and a few brands of yogurt and orange j uice. Cheese
naturall y contains small amounts of vitamin D.
Incl udes lean meats, poultry, fish, beans, eggs, and nuts.
Fish such as salmon, tuna, and mackerel are very good sources of vitamin D. Small amounts of vitamin D are also found
in beef liver and egg yolks.
Is low in saturated fats, trans fats, cholesterol, salt (sodium}, and added sugars.
Vitamin D is added to some margarines.
Stays within your dail y calorie needs.
For more informat ion about building a healthful diet, refer to the Dietary Guidelines for Americans
(http:/ /www.health.gov/djetaryguidelines/dga2005/document/default.htm) and the U.S. Department of Agriculture's food guidance
system, My Pyramid (http:/ /www.mypyramid. gov).
References
1. Deluca HF, Zierold C. Mechanisms and functions of vitamin D. Nutr Rev 1998;56:54-10. [PubMed abstract]
2. Deluca HF. Overview of general physiologic features and functions of vitamin D. Am j Clin Nut r 2004;80:1689S-96S. [PubMed
abstract]
3. van den Berg H. Bioavailability of vitamin D. Eur j Clin Nutr 1997;51 :576-9. [PubMed abstract]
4. Institute of Medi cine, Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D, and
Fluoride. Washington, DC: National Academy Press, 1997.
5. Cranney C, Horsely T, O'Donnell S, Weil er H, Ooi D, Atkinson S, et al. Effectiveness and safety of vitamin D. Evidence
Report/Technology Assessment No. 158 prepared by the University of Ottawa Evidence-based Practice Center under Contract
No. 290-02.0021. AHRQ Publication No. 07-E013. Rockville, MD: Agency for Heal t hcare Research and Qual ity, 2007. [PubMed
abstract]
6. Goldring SR, Krane S, Avioli LV. Disorders of calcification: osteomalacia and rickets. In: DeGroot Lj, Besser M, Burger HG,
jameson j L, Loriaux DL, Marshall j C, et al., eds. Endocrinology. 3rd ed. Philadelphia: WB Saunders, 1995:1204-27.
7. Favus Mj, Christakos S. Pri mer on the Metabolic Bone Diseases and Disorders of Mineral Metaboli sm. 3rd ed. Phi ladelphia, PA:
Lippincott-Raven, 1996.
8. Holick MF. Evol ution and function of vitami n D. Recent results. Cancer Res 2003; 164:3-28. [PubMed abstract]
9. Hayes CE, Hashold FE, Spach KM, Pederson LB. The immunological functions of the vitamin D endocri ne system. Cell Mol Bioi
2003;49:277-300. [ PubMed abstract]
10. Holick MF. Vitamin D deficiency. N Englj Med 2007;357:266-81. [PubMed abstract]
11 . j ones G. Pharmacokinetics of vitamin D toxicity. Am j Clin Nutr 2008;88:582S-6S. [PubMed abstract]
12. Vieth R, Bischoff-Ferrari H, Boucher Bj, Dawson-Hughes B, Garland CF, Heaney RP, et al. The urgent need to recommend an
i ntake of vitamin D that is effective. Am j Clin Nutr 2007;85: 649-50. [PubMed abstract]
http://dietary-supplements.info.nih.gov/factsheets!VitaminD_pf.asp[l2/l/2009 8:09:29 PM]
Dietary Supplement Fact Sheet: Vitamin D
13. Scientific Advisory Committee on Nutrition. Update on Vitamin D. Position Statement by the Scientific Advisory Committee on
Nutrition. London: The Stationery Office, Limited, 2007.
14. Shepard RM, Deluca HF. Plasma concentrations of vitamin D3 and its metabolites in the rat as influenced by vitamin D3 or
245-hydroxyvitamin D3 intakes. Arch Biochem Biophys 1980;202:43-53. [PubMed abstract]
15. Carter GD. 25-hydroxyvitamin D assays: the quest for accuracy. Clio Chern 2009;55:1300-02.
16. Hollis BW. Editorial: the determination of circulating 25-hydroxyvitamin D: no easy task. j. Clio Endocrinol Metab
2004;89:3149-3151.
17. Lensmeyer GL, Wiebe DA, Binkley N, Drezner MK. HPLC method for 25-hydroxyvitamin D measurement: comparison with
contemporary assays. Clio Chern 2006;52:1120-26. [PubMed abstract]
18. Binkley N, Krueger D, Cowgill CS, Plum L, Lake E, Hansen KE, et al. Assay variation confounds the diagnosis of
hypovitaminosis D: a call for standardization. J Clio Endocrinol Metab 2004;89:3152-57. [PubMed abstract]
19. National Institute of Standards and Technology. NIST releases vitamin D standard reference material, 2009.
20. Wagner CL, Greer FR; American Academy of Pediatrics Section on Breastfeeding; American Academy of Pediatrics Committee
on Nutrition. Prevention of rickets and vitamin D deficiency in infants. children. and adolescents . Pediatrics 2008;122: 11 42-
1152. [PubMed abstract]
21. Yetley EA, Brule D, Cheney MC, Davis CD, Esslinger KA, Fischer PWF, et al. Dietary Reference Intakes for vitamin D:
justification for a review of the 1997 values. Am J Clio Nutr 2009;89:719-27. [PubMed abstract]
22. Institute of Medicine, Food and Nutrition Board. Pietary Reference Intakes for vitamin p and calcium.
23. Ovesen L, Brot (,Jakobsen J. Food contents and biological activity of 25-hydroxyvitamin D: a vitamin D metabolite to be
reckoned with? Ann Nutr Metab 2003;47:1 07-13. [PubMed abstract]
24. Mattila PH, Piironen VI, Uusi-Rauva EJ, Koivistoinen PE. Vitamin D contents in edible mushrooms. J Agric Food Chern
1994;42:2449-53.
25. Outila TA, Mattila PH, Piironen VI, Lamberg-AIIardt CJ E. Bioavailability of vitamin D from wild edible mushrooms
(Cantharellus tubaeformis) as measured with a human bioassay. Am j Clio Nutr 1999;69:95-8. [PubMed abstract]
26. Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in the United States and Canada: current status and data needs. Am
j Clio Nutr 2004;80:171 OS-6S. [PubMed abstract]
27. Holick MF. Vitamin D. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease,
10th ed. Philadelphia: Lippincott Williams & Wilkins, 2006.
28. PenningtonjA, DouglassjS. Bowes and Church's Food Values of Portions Commonly Used. 18th ed. Philadelphia: Lippincott
Williams & Wilkins, 2004.
29. Nutrition Coordinating Center. Nutrition Data System for Research (NDS-R). Version 4.06/34. Minneapolis: University of
Minnesota, 2003.
30. U.S. Department of Agriculture, Agricultural Research Service. USDA Nutrient Database for Standard Reference. Release 22,
2009.
31. Byrdwell we, DeVriesj, Exler J , Harnly JM, Holden J M, Holick MF, et al. Analyzing vitamin Din foods and supplements:
methodologic challenges. Am J Cli o Nutr 2008;88:554S-7S. [PubMed abstract]
32. Holick MF. McCollum Award Lecture, 1994. Vitamin D: new horizons for the 21st century. Amj Clio Nutr 1994;60:619-30.
[PubMed abstract]
33. Holick MF. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin
Endocrinol Diabetes 2002;9:87-98.
34. Wharton B, Bishop N. Rickets. Lancet 2003;362:1389-400. [PubMed abstract]
35. Holick MF. Photobiology of vitamin D. In: Feldman D, PikejW, Glorieux FH, eds. Vitamin D, Second Edition, Volume I.
Burlington, MA: Elsevier, 2005.
36. Wolpowitz D, Gilchrest BA. The vitamin D questions: how much do you need and how should you get it? J Am Acad Dermatol
2006;54:301 -1 7. [PubMed abstract]
37. International Agency for Research on Cancer Working Group on ultraviolet (UV) light and skin cancer. The association of use
of sunbeds with cutaneous malignant melanoma and other skin cancers: a systematic review. Intj Cancer 2006;120:1116-22.
[PubMed abstract]
38. American Academy of Dermatology. Position statement on vitamin D. November 1, 2008.
39. Armas LAG, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in humans. J Clio Endocrinol Metab
2004;89:5387-91. [ PubMed abstract]
40. Houghton LA, Vieth R. The case against ergocalciferol (vi tamin D2) as a vi tamin supplement. Am J Clio Nutr 2006;84:694-7.
[PubMed abstract]
41. Nesby-O' Dell S, Scanlon KS, Cogswell ME, Gillespie C, Hollis BW, Looker AC, et al. Hypovitaminosis D prevalence and
determinants among African-American and white women of reproductive age: thi rd National Health and Nutrition Examination
Survey, 1988-1994. Am j Clio Nutr 2002;76: 187-92. [PubMed abstract]
42. Yetley EA. Assessing the vitamin D status of the US population. Am J Clio Nutr 2008;88:558S-64S. [PubMed abstract]
43. Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitamin D status of the US
population: 1988-1994 compared with 2000-2004. Am J Clio Nutr 2008;88:1519-27. [PubMed abstract]
44. Ginde AA, Liu MC, Camargo J r, CA. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-
2004. Arch Intern Med 2009;169:626-32. [PubMed abstract]
45. National Center for Health Statistics. Analytical note for NHANES 2000-2006 and NHANES III 0988 -1994) 25-hydroxyyitamin D
analysis, 2009.
46. Moshfegh A, Goldman J, Ahuja J, Rhodes D, LaComb R. 2009. What We Eat in America, NHANES 2005-2006: Usual Nutrient
http://dietary-supplements.info.nih.gov/factsheets!VitaminD_pf.asp[l2/l/2009 8:09:29 PM]
Dietary Supplement Fact Sheet: Vitamin D
Intakes from Food and Water Compared to 1997 Dietary Reference Intakes for Vitamin D, Calcium, Phosphorus, and
Magnesium. U.S. Department of Agriculture, Agricultural Research Service. [http://www.ars.usda.gov/ba/bhnrc/fsrg]
47. Biser-Rohrbaugh A, Hadley-Miller N. Vitamin D deficiency in breast-fed toddlers.J Pediatr Orthop 2001;21:508-11. [PubMed
abstract]
48. Chesney R. Rickets: an old form for a new century. Pediatr Int 2003;45: 509-11. [PubMed abstract]
49. Picciano MF. Nutrient composition of human milk. Pediatr Clin North Am 2001 ;48:53-67. [PubMed abstract]
50. Gartner LM, Greer FR, American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D
deficiency: new guidelines for vitamin D intake. Pediatrics 2003:111 :908-10. [PubMed abstract]
51. Weisberg P, Scanlon KS, Li R, Cogswell ME. Nutritional r ickets among children in the United States: review of cases reported
between 1986 and 2003. Am J Clin Nutr 2004;80:16975-7055. [PubMed abstract]
52. American Academy of Pediatrics Committee on Environmental Health. Ultraviolet light: a hazard to chi ldren. Pediatrics
1999;104:328-33. [PubMed abstract]
53. Need AG, Morris HA, Horowitz M, Nordin C. Effects of skin thickness, age, body fat, and sunlight on serum 25-hydroxyvitamin
D. Am J Clin Nutr 1993;58:882-5. [PubMed abstract]
54. Webb AR, Kline L, Holick MF. I nfluence of season and latitude on the cutaneous synthesis of vitamin 03: Exposure to winter
sunlight in Boston and Edmonton will not promote vitamin 03 synthesis in human skin. J Clin Endocrinol Metab 1988;67:373-8.
[PubMed abstract]
55. Webb AR, Pilbeam C, Hanafin N, Holick MF. An evaluation of the relative contributions of exposure to sunlight and of diet to
the circulating concentrations of 25-hydroxyvitamin D in an elderly nursing home population in Boston. Am J Clin Nutr
1990;51 :1075-81. [PubMed abstract]
56. Harris 55, Soteriades E, Coolidge JAS, Mudgal S, Dawson-Hughes B. Vitamin D insufficiency and hyperparathyroidism in a low
income, multiracial, elderly population. J Clin Endocrinol Metab 2000;85:4125-30. [PubMed abstract]
57. Lo CW, Paris PW, Clemens TL, Nolan J, Holick MF. Vitamin D absorption in healthy subjects and in patients with intestinal
malabsorption syndromes. Am J Clin Nutr 1985;42:644-49. [PubMed abstract]
58. Wortsman J, Matsuoka LV, Chen TC, Lu Z, Holick MF. Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr
2000;72:690-3. [PubMed abstract]
59. Vilarrasa N, MaravaiiJ, Estepa A, Sanchez R, Masdevall C, Navarro MA, et al. Low 25-hydroxyvitamin D concentrations in
obese women: their clinical significance and relationship with anthropometric and body composition variables. J Endocrinol
Invest 2007;30:653-8. [PubMed abstract]
60. Malone M. Recommended nutritional supplements for bariatric surgery patients. Ann Pharmacother 2008;42:1851-8. [PubMed
abstract]
61. Compher CW, Badellino KO, Boullatajl. Vitamin D and the bariatric surgical patient: a review. Obes Surg 2008;18:220-4.
[PubMed abstract]
62. Reid IR. The roles of calcium and vitamin Din the prevention of osteoporosis. Endocrinol Metab Clin North Am 1998;27: 389-
98. [PubMed abstract]
63. Heaney RP. Long-latency deficiency di sease: insights from calcium and vitamin D. AmJ Clin Nutr 2003;78:912-9. [PubMed
abstract]
64. Parfitt AM. Osteomalacia and related disorders. In: Avioli LV, Krane SM, eds. Metabolic bone disease and clinically related
disorders. 2nd ed. Philadelphia: WB Saunders, 1990:329-96.
65. LeBoff MS, Kohlmeier L, Hurwitz S, Franklin J, Wright J, Glowackij. Occult vitamin D deficiency in postmenopausal US
women with acute hip fracture. JAMA 1999;251 :1505-11. [PubMed abstract]
66. Kirschstein R. Menopausal hormone therapy: summary of a scientific workshop. Ann Intern Med 2003;138:361-4. [PubMed
abstract]
67. American College of Obstetricians and Gynecologists. Frequently Asked Questions About Hormone Therapy. Nm
Recommendations Based on ACOG's Task Force Report on Hormone Therapy.
68. North American Menopause Society. Role of progestrogen in hormone therapy for postmenopausal women: position statement
of The North American Menopause Society. Menopause 2003;10:113-32. [PubMed abstract]
69. Aloia JF. African Americans, 25-hydroxyvitamin D, and osteoporosis: a paradox. Am J Clin Nutr 2008;88:5455-505. [PubMed
abstract]
70. Davis CD. Vitamin D and cancer: current dilemmas and future research needs. Am J Clin Nutr 2008;88:5655-95. [PubMed
abstract]
71. Davis CD, Hartmuller V, Freedman M, Hartge P, Picciano MF, Swanson CA, Milner JA. Vitamin D and cancer: current dilemmas
and future needs. Nutr Rev 2007;65:S71 -S74. [PubMed abstract]
72. Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, et al. A prospective nested case-control study of
vitamin D status and pancreatic cancer ri sk in male smokers. Cancer Res 2006;66:1 0213-9. [PubMed abstract]
73. Lieberman DA, Prindiville S, Weiss DG, Willett W. Risk factors for advanced colonic neoplasia and hyperplastic polyps in
asymptomatic individuals. JAMA 2003;290:2959-67. [PubMed abstract]
74. Wactawski-Wende J, Kotchen J M, Anderson GL, Assaf AR, Brunner RL, O'Sullivan MJ, et al. Calcium plus vitamin D
supplementation and the risk of colorectal cancer. N Eng I J Med 2006;354:684-96. [PubMed abstract]
75. LappeJM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer
risk: results of a randomized trial. Am J Clin Nutr 2007;85:1586-91. [PubMed abstract]
76. Freedman OM, Looker AC, Chang S-C, Graubard Bl. Prospective study of serum vitamin D and cancer mortality in the United
States. J Natl Cancer I nst 2007;99:1594-602. [PubMed abstract]
77. Davis CD, Dwyer JT. The 'sunshine vitamin': benefits beyond bone? J Nat I Cancer Inst 2007;99:1563-5. [PubMed abstract]
http://dietary-supplements.info.nih.gov/factsheets!VitaminD_pf.asp[l2/l/2009 8:09:29 PM]
Dietary Supplement Fact Sheet: Vitamin D
78. Hypponen E, Uiara E, Reunanen A, jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort
study. Lancet 2001 ;358: 1500-3. [PubMed abstract]
79. Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett we, Manson J E, et al. Vitamin D and calcium intake in relation to
type 2 diabetes in women. Diabetes Care 2006;29:650-6. [PubMed abstract]
80. KrauseR, BUhring M, HopfenmUIIer W, Holick MF, Sharma AM. Ultraviolet Band blood pressure. Lancet 1998;352:709-10.
[PubMed abstract]
81. Chiu KC, ChuA, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin
Nutr 2004;79:820-5. [PubMed abstract]
82. Munger KL, Levi n LI, Hollis BW, Howard NS, Asche rio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA
2006;296:2832-8. [PubMed abstract]
83. Merlino LA, Curtis J, Mikuls TR, Cerhan J R, Criswell LA, Saag K. Vitamin D intake is inversely associated with rheumatoid
arthritis: results from the Iowa Women's Health Study. Arthritis Rheum 2004;50:72-7. [PubMed abstract]
84. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine
profi les in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr
2006;83:754-9. [PubMed abstract]
85. Chung M, Balk EM, Brendel M, IpS, Lauj, Leej, et al. Vitamin D and calcium: a systematic review of health outcomes.
Evidence Report/Technology Assessment No. 183 prepared by the Tufts Evidence-based Practice Center under Contract No.
290-2007-10055-I. AHRQ Publication No. 09-E015. Rockville, MD: Agency for Healthcare Research and Quality, 2009.
86. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized control led t rials. Arch
Intern Med 2007;167:1730-7. [PubMed abstract]
87. Giovannucci E. Can vitamin D reduce total mortality? Arch Intern Med 2007;167:1709-10. [PubMed abstract]
88. Chesney RW. Vitamin D: can an upper limit be defined?J Nutr 1989;119 (12 Suppl):1825-8. [PubMed abstract]
89. jackson RD, LaCroix AZ, Gass M, Wallace RB, RobbinsJ, Lewis CE, et al. Calcium plus vitamin D supplementation and the risk
of fractures. N Engl J Med 2006;354:669-83. [PubMed abstract]
90. HathcockJN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. AmJ Clin Nutr 2007;85:6-18. [PubMed abstract]
91. Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM. Calcium and vitamin D3 supplementation prevents bone loss in the
spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-
controlled trial. Ann Intern Med 1996;125:961-8. [PubMed abstract]
92. Lukert BP, Raisz LG. Glucocorticoid- induced osteoporosis: pathogenesis and management. Ann Intern Med 1990;112:352-64.
[PubMed abstract]
93. de Sevaux RGL, Hoitsma AJ, Carstens FHM, Wetzels J FM. Treatment with vitamin D and calcium reduces bone loss after renal
transplantation: a randomized study. J Am Soc Nephrol 2002;13:1608-14. [PubMed abstract]
94. McDuffie J R, Calis KA, Booth SL, Uwaifo GI, Yanovski JA. Effects of orlistat on fat-soluble vitamins in obese adolescents.
Pharmacotherapy 2002;22:814-22. [PubMed abstract]
95. Compston J E, Horton LW. Oral 25-hydroxyvitamin D3 i n treatment of osteomalacia associated with ileal resection and
cholestyramine therapy. Gastroenterology 1978;74:900-2. [PubMed abstract]
96. Gough H, Goggin T, Bissessar A, Baker M, Crowley M, Callaghan N. A comparative study of the relative infl uence of different
anticonvulsant drugs, UV exposure and diet on vitamin D and calcium metabolism in outpatients with epilepsy. Q J Med
1986;59:569-77. [PubMed abstract]
Disclaimer
Reasonable care has been taken in preparing this document and the information provided herein is believed to be accurate.
However, this i nformation is not intended to constitute an "authoritative statement" under Food and Drug Administration rules
and regulations.
About ODS
The mission of the Office of Dietary Supplements (ODS) is to strengthen knowledge and understanding of dietary supplements by
evaluating scientific information, stimulating and supporting research, disseminating research results, and educating the public to
foster an enhanced quality of life and health for the U.S. population.
General Safety Advisory
Health professionals and consumers need credible i nformat ion t o make thoughtful decisions about eating a healthful diet and
using vitamin and mineral supplements. These Fact Sheets provide responsible information about the role of vitamins and
minerals in health and disease. Each Fact Sheet in this series received extensive review by recognized experts from the academic
and research communities.
The information is not intended to be a substitute for professional medical advice. It is important to seek the advice of a
physician about any medical condition or symptom. It is also important to seek t he advice of a physician, registered dietitian,
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Dietary Supplement Fact Sheet: Vitamin D
pharmacist, or other qualified health professional about the appropriateness of taking dietary supplements and their potential
interactions with medications.
Offi ce of Dietary Supplements
National Insti tutes of Health
Bethesda. Maryland 20892 USA
Web: ht!D:I/ods ad njh goy
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PREVENTING CHRONIC DISEASE
PUBLIC HEALTH RESEARCH , PRACTICE , AND POLICY
VOLUME 5: NO. 4 OCTOBER 2008
ORIGINAL RESEARCH
Enforcement of State Indoor Tanning Laws
in the United States
Joni A. Mayer, PhD, Katherine D. Hoerster, BA, Latrice C. Pichon, MPH, Debra A. Rubio, BA,
Susan I. Woodruff, PhD, Jean L. Forster, PhD, MPH
Suggested citation for this article: Mayer JA. Hoerster
KD, Pichon LC. Rubio DA, Woodruff SI, Forster JL.
Enforcement of state indoor tanning laws in the United
States. Prev Cluonic Dis 2008;5(4). http://ll\rww.cdc.gov/
pcd/issues/2008/oct/07 _ 0194. htm. Accessed [date].
PEER REVIEWED
Abstract
Introduct ion
Twenty-eight US states have passed legislation for
indoor tanning facilities. To our knowledge, whether
these state laws are actually enforced has not been
evaluated previously in all 28 states. Therefore, we
interviewed key informants in these states to assess
enforcement practices.
Methods
Two trained interviewers used a structured survey
instrument to interview 28 key informants who were
knowledgeable about enforcement practices for laws
regarding indoor tanning. Respondents provided informa-
tion specific to the most populous city in their states.
Results
Licensure for indoor tanning businesses was required
in 22 of the 28 cities. Slightly less than half of the cities
gave citations to tanning facilities that violated state law.
Approximately 32% of the cities did not inspect indoor tan-
ning facilities for compliance with state law, and another
32% conducted inspections less t han annually. Of t hose
cities that inspected at all, most conducted unannounced
inspections.
Conclusion
The relatively low rates of annual inspections and cita-
tions are of concern. We recommend that future studies
assess whether legislation, enforcement practices, or a
combination of the 2 affects the practices of indoor tanning
facilities or of consumers.
Introduction
Indoor tanning with UV radiation lamps has been
linked to melanoma (1), squamous cell carcinoma (1),
molecular damage associated with skin cancer (2), and
other acute damage to eyes and skin (3,4). Commercial
indoor tanning facilities are prevalent in the United
States (5), and "all-you-can-tan" discount pricing pack-
ages make indoor tanning inexpensive (6). The rates of
indoor tanning for teen girls in the United States are
high (7-10); in a national sample, approximately 40% of
17- to 18-year-old girls had used indoor tanning in the
past year (7).
Some US states have passed legislation regulating
indoor tanning facilities, with the intent of reducing risks
to consumers. Ongoing systematic updates on the number
and content of these laws have been provided, focusing on
youth access restrictions (11-13). A recent report quanti-
fied the stringency of state indoor tanning legislation in
the 28 states that had a state law as of2006 (14). However,
in order to assess the level at which the laws are imple-
mented and the effect of these laws on the industry and
consumers, information about enforcement practices is
needed. Consequently, we conducted telephone interviews
of key informants in states with indoor tanning legislation
to assess enforcement practices.
The opinions expressed by authors contributing to this journal do not necessarily reflect the opinions of the US Department of Health and Human Serv1ces,
the Public Health Serv1ce, the Centers for D1sease Control and Prevention, or the authors' affiliated mstitut1ons. Use of trade names IS for identification only
and does not imply endorsement by any of the groups named above.
www.cdc.gov/pcd/issues/2008/ocV07 _0194.htm Centers for Disease Control and Prevention 1
PREVENTING CHRONIC DISEASE
VOLUME 5: NO. 4
OCTOBER 2008
PUBLIC HEALTH RESEARCH , PRACTICE , AND POLICY
Methods
Settings and participants
The CITYlOO (Correlates of Indoor Tanning in Youth)
project assesses factors that may influence use of indoor
tanning by adolescents (10,14); 1 objective is to better
understand current legislation that pertains to indoor tan-
ning. In the current study, we targeted the most populous
city in each of the 28 states to evaluate how state laws are
enforced at the local level.
Our goal was to interview, by telephone, the person who
was t he most knowledgeable about enforcement prac-
tices in each city or county. From a list of contacts for each
state's legislation presented on a Web site operated by the
tanning industry (15), we telephoned these contacts (typi-
cally at the state or county health department) and asked
them to identify the best key informant. The process for
identifying each city's respondent continued until we found
a knowledgeable potential 1espondent. We then mailed
an introductory letter to each potential respondent that
explained the purpose ofthe study and its voluntary nature
and assured anonymity of t he respondent and that data
would not be linked to the city's name in any published
reports. Approximately 1 week after mailing the letter, we
attempted to contact informants until we reached them
and they completed the interview. The 2 interviewers
(K.D.H. and L.C.P.) had previous experience in conducting
telephone interviews and received training for this study.
Survey
The survey questions were based on a combination of
previous study in this area (16), expert opinion about mea-
suring enforcement activities in the tobacco control area
(a good model for indoor tanning), and select enforcement
and monitoring activities mentioned in the indoor tanning
laws (14). Initially, we developed a longer version of the
survey that asked for specific data on various activities
(eg, number of facilities inspected in the previous year,
number of complaints received). That version assumed a
high level of inspection and other enforcement activities,
assumed that enforcement agencies kept detailed records
of those activities, and requested that informants obtain
that information before the interview and provide it during
the interview. During the informant identification process,
we became aware that the level of enforcement activities
was fairly low. Therefore, to better match the depth of our
assessment to actual practices, reduce the amount of work
required of respondents, and achieve a higher response
rate, we retained only the basic items and eliminated the
more elaborate, labor-intensive items.
The following factors were assessed: number of staff allo-
cated to carry out enforcement activities in the city/county;
whether indoor tanning businesses were required to have
a license; frequency of inspections (in absence of a com-
plaint); whether inspections were announced in advance;
whether inspection included review of customer records
and, if so, whether customer's age, parental consent forms,
number and dates of tanning sessions, and duration of
sessions were examined; and whether businesses received
citations when they violated the law. We also assessed the
types of penalties for selling sessions to underage youth or
not obtaining parental permission for minors and whether
graduated penalties (more severe penalties for each suc-
cessive violation) were used. A copy of the survey is pro-
vided in the Appendix.
A draft of the survey was reviewed for clarity by 2 public
health department professionals. All survey procedures
and materials were approved by t he institutional review
borud at San Diego State University. Interviews were con-
ducted in April and May of 2007.
Statistical analysis
Descriptive statistics, including frequencies or means,
were computed for each vruiable. Additionally, we con-
ducted bivariate tests (x
2
and correlations) to assess the
associations between the stringency of the written law (14)
and reported enforcement practices. Specifically, we exam-
ined the relationship between reported inspection fiequen-
cy and overall law stringency score, youth access subscore,
enforcement subscore, and 1 individual inspection item.
For the items about penalties specific to youth access, we
computed frequencies for only the 21 cities in states with
youth access laws. We did not perform multivariate tests
because of the small sample size. All analyses were con-
ducted in SPSS 13.0 (SPSS Inc, Chicago, Illinois).
Results
Response rates and respondent characteristics
We identified 28 respondents (1 for the most populous
The opinions expressed by authors contributing to th1s journal do not necessarily reflect the opinions of the US Department of Health and Human Serv1ces,
the Public Health S e r v ~ c e the Centers for D1sease Control and Prevention, or the authors' affiliated mstitutlons. Use of trade names is for identification only
and does not imply endorsement by any of the groups named above.
2 Centers for Disease Control and Prevention www.cdc.gov/pcd/issues/2008/ocV07 _0194.htm
PREVENTING CHRONIC DISEASE
VOLUME 5: NO. 4
OCTOBER 2008
PUBLIC HEALTH RESEARCH , PRACTICE , AND POLICY
city in each of the 28 targeted states) who confirmed that
they were knowledgeable about enforcement practices.
Data were obtained for all 28 cities. If respondents told
the interviewer that their states had no law (n = 5) or that
the cities engaged in no enforcement activities (n = 2), the
interviewer contacted additional informants to confirm
that laws were not enforced. The interviewer then coded
the remaining survey items to indicate nonperformance of
enforcement activities.
Enforcement resources and practices
More than three-fourths of the respondents were
employed by a state or local health agency (Table 1). The
organizations that employed the respondents also consti-
tuted the primary enforcement entity for the state indoor
tanning legislation in the designated city.
The number of full-time employees available for inspec-
tions and other enforcement activities ranged from 0 to 15,
with a mean of 3.29 (standard deviation 3.89) staff and a
median of 2. Approximately 29% of the cities had no full-
time enforcement staff (Table 2). Licensure for indoor tan-
ning businesses was required in most cities. Slightly less
than half of the cities gave citations (ie, penalties) to tan-
ning facilities that violated the state law. Approximately
32% of the cities did not inspect indoor tanning facilities
for compliance with the state law, and another 32% con-
ducted inspections less than annually. Of those cities that
inspected, most conducted unannounced inspections.
Of the 19 cities that conducted inspections, most reviewed
customer records as part of the inspection process. Of
these, most reviewed information about customers' ages,
parental consent forms, number and dates of tanning ses-
sions, and tanning session duration (Table 3).
Of the 21 cities in states that had youth access laws,
approximately half penalized these violations (Table 4).
Warnings, monetary fines, and license suspensions were
used for both kinds of youth access violations, with no
strong predominance by type of penalty. Of the cities that
penalized violations, most gave graduated penalties for
each of the youth access- related violations, in which each
additional violation results in a larger penalty.
Bivariate associations
We conducted Pearson correlational tests between
inspection frequency and the variables from an earlier
assessment of state indoor tanning laws (14). These cor-
relations (N = 28) were 0.51 (P = .006) for enforcement
subscore, 0.34 (P = .075) for minor's access stringency sub-
score, and 0.58 (P = .001) for overall law stringency score.
Reported inspection frequency was positively correlated
with the number of full-time enforcement staff reported
by the respondent (r = 0.48, P = .Oll). We then dichoto-
mized reported inspection frequency (less than annually
vs at least annually) and the individual inspection item
score from the earlier analysis of state laws (less strict vs
more strict) . These variables were significantly associated
(x
2
= 5.18, P = .023) . Of cities whose laws on inspections
were less strict (n = 21), only 23.8% conducted inspections
at least annually. Of those whose inspection requirement
was stricter (n = 7), 71.4% conducted inspections at least
annually. A license requirement in the written law was
significantly associated with actual (self-reported) license
requirement (x
2
= 5.06, P = .024). In cities in which the
state law did not mention licensure (n = 6), 50% required
licensure, whereas in cities whose law mentioned licensure
(n = 21), 90.5% required licensure.
Discussion
To our knowledge, this article is 1 of only 3 to report
actual enforcement practices related to state indoor tan-
ning laws (16, 17) and the only article to date that pro-
vides enforcement information for all 28 states. Our data
indicate that routine annual inspections, which are a pre-
requisite for other enforcement activities such as levying
penalties for violations, are not conducted in 64% of the cit-
ies. However, for those cities that conduct regular inspec-
tions, most conduct unannounced inspections, which likely
increases their effectiveness. Additionally, the annual
inspections routinely included review of client records and
encompassed information that may reflect UV radiation
exposure levels (eg, duration and frequency of sessions)
and youth access (eg, customer age and parental consent
forms) . Thus, the annual inspections appear to be of high
quality. The relationship between inspection frequency
and staffing level suggests that cities that do not conduct
annual inspections need more resources. However, we can-
not infer causality because of the study's cross-sectional
design. Results from a study of sanitarians within 1 large
metropolitan area in both Massachusetts (21 munici-
palities of Boston) and Minnesota (21 jurisdictions of the
Twin Cities) indicated the rates of routine inspections
The opinions expressed by authors contributing to th1s journal do not necessarily reflect the opinions of the US Department of Health and Human Serv1ces,
the Public Health S e r v ~ c e the Centers for D1sease Control and Prevention, or the authors' affiliated mstitutlons. Use of trade names is for identification only
and does not imply endorsement by any of the groups named above.
www.cdc.gov/pcd/issues/2008/ocV07 _0194.htm Centers for Disease Control and Prevention 3
PREVENTING CHRONIC DISEASE
VOLUME 5: NO. 4
OCTOBER 2008
PUBLIC HEALTH RESEARCH , PRACTICE , AND POLICY
by Massachusetts agencies were higher than those in
Minnesota (89.9% vs 28.6%) (16). Responses from state
health department staff in Texas, lllinois, and Wisconsin
showed a large amount of variability (for each state as a
whole) on both penalties to facilities for youth access viola-
tions and facility inspection/auditing practices (17).
The low rates of penalizing any violation and youth
access violations are also cause for concern. As is the case
with enforcement activities regarding tobacco and alcohol
control, businesses rue less likely to comply with age-of-
sale laws if noncompliance is not penalized (18, 19).
The strong association between various aspects of the
law and enforcement activities is encouraging. However,
in the 7 states with more stringent inspection require-
ments, the inspection requirements tended to overestimate
the actual level of inspections. Moreover, 5 respondents
incorrectly reported that their states, at the time of the
interview, had no law on indoor tanning. Therefore, even
though some states had laws, they were not being enforced
even minimally.
One limitation of this study is that the data were based
on the report of enforcement professionals, and we did
not attempt to verify them with other measures such as
interviews with tanning facility managers. Although we
assured their anonymity, respondents may have over-
reported enforcement practices. Second, we used the most
populous city in each state to represent enforcement of the
state law, so our findings may not generalize to other cit-
ies and rural areas in each state. Initially, in 18 of the 28
states, we interviewed participants about the enforcement
practices of at least 1 additional large city in that state.
However, because the key enforcement practices were
almost perfectly consistent between cities in each state, we
ultimately used the "largest city in state" approach. That
experience leads us to believe that the data for each city
generalize to other large cities in each state. Finally, we
neglected to ask about each state's licensing fees, if any;
such fees could help fund enforcement activities (20).
Strengths of our study included an optimal response
rate and our access to reliable data on the stringency of
each state's law (14) . These data facilitated compruisons
between "ideal" and "real" enforcement activities. As noted
earlier, we promised respondents that we would not link
published data to individuals or cities; this assurance of
anonymity probably improved both our response rate and
the accuracy of the data. Even though we are unable to
reveal which states were enforcing at lower levels, we will
be providing each respondent with feedback on how the
city's enforcement level compares with enforcement for all
other cities combined. For states in which enforcement is
low, the feedback may increase enforcement practices.
In tobacco control, antitobacco organizations historically
focused their efforts on passing new laws, but enforcement
of existing laws is viewed by many to have been critical to
reducing tobacco use (21-26). In the field of indoor tanning
legislation, we cannot say whether legislation, enforce-
ment practices, or a combination of the 2 has any effect on
the practices of indoor tanning facilities or of consumers.
Therefore, we recommend that future evaluations of indoor
tanning legislation measure not only the Wl"itten law but
also its implementation and enforcement; research should
also attempt to assess the relationship between legislation
strictness/enforcement level and the practices of business-
es and consumers, especially adolescent consumers.
Acknowledgments
This study was supported by the National Cancer Institute,
grants R01 CA093532, R01 CA093532S1, and K05 100051.
The following were partially responsible for study concept
and design: Dr George Belch, Dr James Sallis, Dr Donald
Slymen, Ms Elizabeth Clapp, and Ms Rebecca Garrow,
San Diego State University; Dr Todd Gilmer, University
of California Medical School, San Diego; and Dr Mrutin
Weinstock, Veterans Administration Medical Center and
Brown University. We thank Ms Lorri Freitas of the San
Diego County Health and Human Services Agency and Dr
Donald Bishop of the Minnesota Department of Health for
valuable feedback on the survey instrument and the survey
participants for their time and effort.
Author Information
Corresponding Author: Joni A. Mayer, PhD, Graduate
School of Public Health, San Diego State University, 9245
Sky Pruk Ct, Ste 220, San Diego, CA 92123. Telephone:
619-594-7916. E-mail: jmayer@mail.sdsu.edu.
Author Affiliations: Katherine D. Hoerster, J oint Doctoral
Program in Clinical Psychology, Latrice C. Pichon, Joint
Doctoral Program in Public Health, Health Behavior, San
The opinions expressed by authors contributing to th1s journal do not necessarily reflect the opinions of the US Department of Health and Human Serv1ces,
the Public Health S e r v ~ c e the Centers for D1sease Control and Prevention, or the authors' affiliated mstitutlons. Use of trade names is for identification only
and does not imply endorsement by any of the groups named above.
4 Centers for Disease Control and Prevention www.cdc.gov/pcd/issues/2008/ocV07 _0194.htm
PREVENTING CHRONIC DISEASE
VOLUME 5: NO. 4
OCTOBER 2008
PUBLIC HEALTH RESEARCH , PRACTICE , AND POLICY
Diego State University/University of California, Debra
A. Rubio, Susan I. Woodruff, School of Social Work, San
Diego State University, San Diego, California; J ean L.
Forster, School of Public Health, University of Minnesota,
Minneapolis, Minnesota. At the time of this 1esearch,
Susan I. Woodruff was affiliated with the Graduate School
of Public Health, San Diego State University, San Diego,
California.
References
1. International Agency for Research on Cancer, working
group on artificial ultraviolet (UV) light and skin can-
cer. The association of use of sunbeds with cutaneous
malignant melanoma and other skin cancers: a sys-
tematic review. [Published erratum in: Int J Cancer
2007;120(11):2526]. Int J Cancer 2007;120(5):1116-
22.
2. Whitmore SE, Morison WL, Potten CS, Chadwick C.
Tanning salon exposure and molecular alterations. J
Am Acad Dermatol 2001;44(5):775-80.
3. Centers for Disease Control and Prevention. Injuries
associated with ultraviolet tanning devices- Wisconsin.
MMWR Morb Mortal Wkly Rep 1989;38(19):333-5.
4. Walters BL, Kelley TM. Commercial tanning facili-
ties: a new source of eye injury. Am J Emerg Med
1987;5(5):386-9.
5. Palmer RC, Mayer JA, Woodruff SI, Eckhardt L, Sallis
JF. Indoor tanning facility density in eighty US cities.
J Community Health 2002;27(3):191-202.
6. Kwon HT, Mayer JA, Walker KK, Yu H, Lewis EC,
Belch GE. Promotion of flequent tanning sessions
by indoor tanning facilities: two studies. J Am Acad
Dermatol 2002;46(5):700-5.
7. Cokkinides VE, Weinstock MA, O'Connell MC, Thun
MJ. Use of indoor tanning sunlamps by US youth,
ages 11-18 years, and by their parent or guard-
ian caregivers: prevalence and correlates. Pediatrics
2002; 109(6): 1124-30.
8. Demko CA, Borawski EA, Debanne SM, Cooper KD,
Stange KC. Use of indoor tanning facilities by white
adolescents in the United States. Arch Pediatr Adolesc
Med 2003;157(9):854-60.
9. Geller AC, Colditz G, Oliveria S, Emmons K, Jorgensen
C, Aweh GN, et al. Use of sunscreen, sunburning rates,
and tanning bed use among more than 10,000 US chil-
dren and adolescents. Pediatrics 2002;109(6):1009-14.
10. Hoerste1 KD, Mayer JA, Woodruff SI, Malcarne V,
Roesch SC, Clapp E. The influence of pruents and
peers on adolescent indoor tanning behavior: find-
ings flom a multi-city sample. J Am Acad Dermatol
2007;57(6):990-7.
11. Dellavalle RP, Parker ER, Cersonsky N, Hester EJ,
Hemme B, Burkhardt DL, et al. Youth access laws:
in the dark at the tanning parlor? Arch Dermatol
2003; 139( 4):443-8.
12. Francis SO, Burkhardt DL, Dellavalle RP. 2005: a
banner year for new US youth access tanning restric-
tions. Arch Dermatol2005; 141(4):524-5.
13. McLaughlin JA, Francis SO, Burkhardt DL, Dellavalle
RP. Indoor UV tanning youth access laws: update
2007. Arch Dermatol 2007;143(4):529-32.
14. Woodruff SI, Pichon LC, Hoerster KD, Forster JL,
Gilmer T, Mayer JA. Measuring the stringency of states'
indoor tanning regulations: instrument development
and outcomes. JAm Acad Dermatol 2007;56(5):774-
80.
15. A guide to state radiation control offices. Phoenix (AZ):
National Tanning Training Institute. http://www.
tanningtraining .com/reginfo/sta te.h tml. Accessed
September 25, 2006.
16. Hickle A, Forster J , Lazovich D, Allwood P, Remba
N, Grossmeier J, et al. Sanitarians' work with indoor-
tanning businesses: findings from interviews in
two major metropolitan areas. J Environ Health
2005;67(8):30-6, 54.
17. Hester EJ, Heilig LF, D'Ambrosia R, Drake AL,
Schilling LM, Dellavalle RP. Compliance with youth
access regulations for indoor UV tanning. Arch
Dermatol 2005;141(8):959-62.
18. Dent CW, Grube JW, Biglan A. Community level alco-
hol availability and enforcement of possession laws as
predictors of youth drinking. Prev Med 2005;40(3):355-
62.
19. Forster JL, Wolfson M. Youth access to tobacco: poli-
cies and politics. Annu Rev Public Health 1998;19:203-
35.
20. Demierre MF. Time for national legislation of
indoor tanning to protect minors. Arch Dermatol
2003;139:520-4.
21. Forster JL, Komro KA, Wolfson M. Survey of city ordi-
nances and local enforcement regarding commercial
availability of tobacco to minors in Minnesota, United
States. Tob Control1996;5(1):46-51.
22. Jacobson PD, Wasserman J. The implementation and
enforcement of tobacco control laws: policy implica-
tions for activists and the industry. J Health Polit
The opinions expressed by authors contributing to th1s journal do not necessarily reflect the opinions of the US Department of Health and Human Serv1ces,
the Public Health S e r v ~ c e the Centers for D1sease Control and Prevention, or the authors' affiliated mstitutlons. Use of trade names is for identification only
and does not imply endorsement by any of the groups named above.
www.cdc.gov/pcd/issues/2008/ocV07 _0194.htm Centers for Disease Control and Prevention 5
PREVENTING CHRONIC DISEASE
VOLUME 5: NO. 4
OCTOBER 2008
PUBLIC HEALTH RESEARCH , PRACTICE , AND POLICY
Policy Law 1999;24(3):567-98.
23. Jason LA, Porkorny SB, Schoeny ME. Evaluating the
effects of enforcements and fines on youth smoking.
Critical Public Health 2003; 13:33-45.
24. Lazovich D, Forster J, Widome R, VanCoevering P.
Tobacco possession, use, and purchase laws and pen-
alties in Minnesota: enforcement, tobacco diversion
programs, and youth awareness. Nicotine Tob Res
2007;9(Suppl1):S57-64.
25. Ma GX, Shive S, Tracy M. The effects of licensing
and inspection enforcement to reduce tobacco sales
to minors in greater Philadelphia, 1994-1998. Addict
Behav 2001;26(5):677-87.
26. Woodhouse LD, Sayre JJ, Livingood WC. Tobacco
policy and the role of law enforcement in prevention:
the value of understanding context. Qual Health Res
200 1; 11(5):682-92.
Tables
Table 1. Respondent and Organization Characteristics (N =
28), CITY100 Enforcement Survey, April and May 2007
Variable n (%)
Sex
-
Women 7 (25.0)
Men 21 (75.0)
Organization
State health, environmental health, or radiologic health 15 (53.6)
agency
City or county health, environmental health, or radiologic 7 (25.0)
health agency
State cosmetology board 4 (14.3)
Other state agency 2 (7.1)
Occupation/title
Department head or director 6 (21.4)
- -- -
Supervisor or manager 6 (21.4)
Health physicist 4 (14.3)
Environmental health or industrial hygiene 3 (10.7)
-
Sanitarian 3 (10. 7)
Inspector 2 (7.1)
L Other"
-
4 (14.3)
Abbreviat ion: CITY100, Correlates of Indoor Tanning in Youth.
a These titles included investigator, board administrator, regulatory enforce
ment, and compliance officer.
The opinions expressed by authors contributing to th1s journal do not necessarily reflect the opinions of the US Department of Health and Human Serv1ces,
the Public Health S e r v ~ c e the Centers for D1sease Control and Prevention, or the authors' affiliated mstitutlons. Use of trade names is for identification only
and does not imply endorsement by any of the groups named above.
6 Centers for Disease Control and Prevention www.cdc.gov/pcd/issues/2008/ocV07 _0194.htm
PREVENTING CHRONIC DISEASE
PUBLIC HEALTH RESEARCH , PRACTICE, AND POLICY
VOLUME 5: NO. 4
OCTOBER 2008
Table 2. Indoor Tanning Legislation Enforcement Resources and General Practices (N = 28), CITY100 Enforcement Survey,
April and May 2007
Variable
No. of full-time enforcement staff
0
1-2
3-4
2:5
1-
Ucensure required
No
1-
Yes
Don't know
Give citation if facility violates law
No
Yes
Don't know
Inspection schedule
Never
Less than annually
Annually
1-
Twice a year
Announce inspection in advance
8
1-
Never/rarely
Sometimes
Often/always
Abbreviation: CITY100, Correlates of Indoor Tanning in Youth.
a Based on the 19 cities that ever conducted inspections.
n (%)
8 (28.6)
7 (25.0)
7 (25.0)
6 (21.4)
-
5 (17.9)
22 (78.6)
1 (3.6)
r
14 (50.0)
13 (46.4)
1 (3.6)
-
9 (32.1)
9 (32.1)
6 (21.4)
-
4 (14.3)
17 (89.5)
2 (10.5)
1
0
-
The opinions expressed by authors contributing to th1s journal do not necessarily reflect the opinions of the US Department of Health and Human Serv1ces,
the Public Health Serv1ce, the Centers for D1sease Control and Prevention, or the authors' affiliated mstitutlons. Use of trade names is for identification only
and does not imply endorsement by any of the groups named above.
www.cdc.gov/pcd/issues/2008/ocV07 _0194.htm Centers for Disease Control and Prevention 7
PREVENTING CHRONIC DISEASE
PUBL I C HEALT H RESEARCH, PRACTICE, AND POLICY
VOLUME 5: NO. 4
OCTOBER 2008
Table 3. Indoor Tanning Facility Inspection Practices Related to Customer Records, CITY100 Enforcement Survey, April and
May 2007
Frequency
--------------------------------------------
Practice
Inspection includes customer record review"
Review includes customer's ageb
Review includes parental consent formsb
1--
Review includes number and dates of sessionsb
Review includes session duration!>
Abbreviation: CI1Y100, Correlates of Indoor Tanning in Youth.
a Based on the 19 cities t hat ever conducted inspections.
b Based on the 17 cities t hat included customer record review when inspecting.
Never/Rarely
n (%)
2 (10.5)
1 (5.9)
2 (11.8) l
1 (5.9)
2 (11.8)
Sometimes Often/Always
n (%) n (%)
2 (10.5) 1 15 (78.9) 1
0 16 (94.1)
0 15 (88.2)
-
3 (17.6) 13 (76.5)
1 (5.9) 14 (82.4)
Table 4. Penalties for Youth Access Violations in States With Indoor Tanning Access Laws, CITY100 Enforcement Survey, April
and May, 2007
Violation
-------------------------------------------------------------------
Selling Sessions to Underage Youth Not Obtaining Parental Consent for Minors
Penalty n (%)" n (%)b
Penalty type
Any type 11 (55.0) 10 (47.6)
Warning 10 (50.0) 9 (42.9)
Monetary fine 8 (40.0) 8 (38.1)
License suspension 7 (35.0) 7 (33.3)
Other 3 (15.0) 1 (4.8)
Graduated penalties given
I
No 4 (36.4) I 3 <3o.o> I
Yes
-
Abbreviation: CITY100, Correlates of Indoor Tanning in Youth.
a Based on 20 respondents because of missing data.
b Based on 21 respondents.
c Based on those respondents whose cities gave any type of penalty for the violation.
7 (63.6) I 7 (70.0)
The opinions expressed by authors contributing to th1s journal do not necessarily reflect the opinions of the US Department of Health and Human Serv1ces,
the Public Health Serv.ce, the Centers for D1sease Control and Prevention, or the authors' affiliated mstitutlons. Use of trade names is for identification only
and does not imply endorsement by any of the groups named above.
8 Centers for Disease Control and Prevention www.cdc.gov/pcd/issues/2008/ocV07 _0194.htm
PREVENTING CHRONIC DISEASE
VOLUME 5: NO. 4
OCTOBER 2008
PUBLIC HEALTH RESEARCH , PRACTICE , AND POLICY
Appendix: CI1Y100 Enforcement Survey
Study Introduction
This interview is part of the CITYiOO Indoor Tanning Project. CITYiOO
(Correlates of Indoor Tanning in Youth) is a project funded by the National
Cancer Institute that will help us better understand the factors that influ
ence teens to use indoor tanning. The project is based at the Graduate
School of Public Health at San Diego State University and is focusing on
over iOO cities in the US. One goal of CITYiOO is t o evaluate enforcement
activities in cities located in states with indoor tanning laws. Your state has
a law governing indoor tanning.
If you decide to participate, I will ask you questions about the enforcement
activities in [city/county]. such as inspections of indoor tanning facilities.
These are activities at the city or county level to enforce the state
law. We would like you to participate, irrespective of whether your city has
many or few enforcement activities. The interview will take only around 5
to 7 minutes. The researcher in charge of this study is Dr Joni Mayer; you
may have her phone number if you wish to write it down. Collect calls are
accepted. She will be able to answer any questions you have. Or if you
have any questions now, I can answer them for you. I want to assure you
that your responses in this interview wil l not be linked with your narne.
city, or county in any written reports or publications. All data will be kept in
locked file cabinets, and only the CITYiOO research staff will have access
to the data. Participation is voluntary, and you are free to end the interview
at any point.
Resources (R)
I'd like to first ask you about your employment, and [city'S/county's)
resources related to regulating indoor tanning businesses.
Ria. What is the agency you work for?
Ri b. What department within that agency?
Ric. Is your job at the
City level?
County level?
State level?
None of these? Describe.
R2. What is your occupation and/or j ob title?
R3. How many agencies are responsible for enforcing the state's indoor
tanning law in [city/county]?
None/no enforcement
One
Two or more
Don' t know
Refused
No state law
R4. The primary enforcement agency-is it at the
City-level? Name:
County-level? Name:
Statelevel? Name:
None of these? Name:
R5. How many full-time staff (or FTE) are allocated to carry out the inspec-
tions and/or other enforcement activities in [city/county]?
Gave a number:
Don't know
Refused
Not applicable
Licensure (L)
Li. Are indoor tanning businesses in [city) required to have a license?
No
Yes
Don't know
Refused
Not applicable
Inspections (I)
Now I'd like to ask you about inspection procedures.
li. In the absence of a complaint, how often is a tanning facility inspected
in [city/county]?
Never (go to question P1)
Less than once a year
Once a year
Twice a year
More than twice a year
Other (describe)
Don't know
Refused
Not applicable
12. How often is the inspection announced in advance to the tanning facility
t hat will be inspected?
Never/ rarely
Sometimes
Often/always
Don't know
Refused
Not applicable
13. Please tell me how often an inspection includes the review of customer
records.
Never/ rarely
Sometimes
Often/always
Don't know
Refused
Not applicable
14. (If the answer to 13 is sometimes, often, or always) When customer
records are reviewed, how often are the following looked at?
14a. Age of customers
Never/ rarely
Sometimes
The opinions expressed by authors contributing to th1s j ournal do not necessarily reflect the opinions of the US Department of Health and Human Serv1ces,
the Public Health Serv1ce, the Centers for D1sease Control and Prevention, or the authors' affiliated mstitutlons. Use of trade names is for identification only
and does not imply endorsement by any of the groups named above.
www.cdc.gov/pcd/issues/2008/ocV07 _0194.htm Centers for Disease Control and Prevention 9
PREVENTING CHRONIC DISEASE
VOLUME 5: NO. 4
OCTOBER 2008
PUBL I C HEALT H RESEARCH , PRACTICE, AND POLICY
Often/always
Don't know
o Refused
o Not applicable
14b. Parental consent forms
o Never/rarely
o Sometimes
o Often/always
o Don't know
Refused
o Not applicable
14c. Number and dates of tanning sessions
o Never/rarely
o Sometimes
o Often/always
Dont know
o Refused
o Not applicable
14d. Duration of tanning sessions
o Never/ rarely
Sometimes
o Often/always
o Don't know
Refused
o Not applicable
Penalties/Fines (P)
The next questions are about penalties for violations of laws regulating
indoor tanning.
Pl. If a tanning facility in [city/county] violates a law regulating this type of
business, will the facility receive a citation?
No (skip the remaining items}
o Yes
Don't know
o Refused
Not applicable
P2. In general, what is the penalty if a facility is cited for selling tanning
sessions to underage youth?
P2a. A warning
. No
Yes
Don't know
Refused
o Not applicable
P2b. A monetary fine
o No
o Yes
o Don't know
o Refused
o Not applicable
P2c. License suspension
No
Yes
o Don't know
Refused
o Not applicable
P2d. Other (probe}
P3. If a facil ity is cited more than once for selling tanning sessions to
underage youth, does [city/county] use graduated penalties, in which
each repeat violation results in a larger penalty?
No
o Yes
Don't know
Refused
Not applicable
P4. In general, what are the penalties if a facility is cited for not obtaining
parental permission for minors?
P4a. A warning
No
. Yes
Don't know
Refused
Not applicable
P4b. A monetary fine
No
o Yes
Don't know
o Refused
Not applicable
P4c. License suspension
No
o Yes
Don't know
Refused
Not applicable
P4d. Other (probe}
P5. If a facility is cited more than once for not obtaining parental permis-
sion, does your city/county use graduated penalties, in which each
repeat violation results in a larger penalty?
No
Yes
Don't know
Refused
o Not applicable
That concludes all my questions. I really appreciate all of your time! Do
you have any questions or comments about this survey? Thanks again.
Goodbye.
The opinions expressed by authors contributing to th1s journal do not necessarily reflect the opinions of the US Department of Health and Human Serv1ces,
the Public Health S e r v ~ c e the Centers for D1sease Control and Prevention, or the authors' affiliated mstitutlons. Use of trade names is for identification only
and does not imply endorsement by any of the groups named above.
10 Centers for Disease Control and Prevention www.cdc.gov/pcd/issues/2008/ocV07 _0194.htm
FEDERAL REGISTER
Vol . 64, No . 26
Proposed Rules
DEPARTMENT OF HEALTH AND HUMAN SERVICES {HHS)
Food and Drug Administration (FDA)
21 CFR Part 1020
[ Docket No . 98N- 1 170 ]
Medi cal Devi ces ; Sunlamp Products Performance Standard; Request fo r
Commentsand Information
64 FR 6288
DATE : Tuesday, February 9, 1999
ACTION : Advance notice o f proposed rulemaki ng .
To vi ew t he next page , type . np* TRANSMIT .
To vi ew a spec i f i c page , t r ansmi t p* and the page number , e . g . p*1
[*6288]
SUMMARY : The Food and Drug Admi nistration {FDA) is announci ng i ts i ntent to
propose amendment s to t he performance standard for sunlamp products . The
agency is t a king thi s act ion to addr ess concer ns about the adequacy of the
warn i ngs on sunlamp p r oduct s , cur r ent recommended exposur e schedule t o
minimize risk to customers who choose to produce and maintain a tan, current
labeling f or replacement l amps , and current heal th warnings which do not
reflect recent advances in photobi o l ogical research . FDA i s sol ici t i ng
comments and i nf ormat i on from interested persons concerning the subject matter
of the proposed amendment s .
DATES : Wri t t en commen t s by May 10, 1999 .
ADDRESSES : Submit written comment s to the Dockets Management Branch {HFA-
305) , Food and Drug Administration, 5630 Fishers Lane , rm. 1061, Rockville , MD
20852. I ndividuals or organizat i ons wishing to receive copies o f draft
amendments or related documents d i s tributed for review during the development
of these amendments may have their names placed on a mailing list by wri t ing
t o Office of Science and Technology (HFZ-114) , Cent er for Devices and
Radi ologi cal Heal th, Food and Dr ug Admi ni s trat i on , 5600 Fi sher s Lane ,
Roc kville , MD 20857 , FAX 301-594-6775, e-mail address HWCCDRH . FDA . GOV.
FOR FURTHER INFORMATION CONTACT : W. Howard Cyr , Cent er for Devices and
Radiological Health (HFZ- 114) , Food and Drug Adminis t ration, 5600 Fishers
Lane , Rockville, MD 20857 , 301- 443- 7179 . [*6289)
SUPPLEMENTARY I NFORMATION :
I . Background
The Safe Medical Devices Act o f 1 990 (Pub . L. 101-629) , enacted on November
28 , 1990, t ransferred t he provisions of t he Radiation Control for Heal t h and
Safet y Act of 1968 (Pub . L. 90- 602) from Title III of t he Public Health
Ser vi ce Ac t t o Chapter V, subchapter C of t he Feder a l Food , Dr ug, and Cosmet i c
Act (21 U. S . C. 360hh et seq . ) . This authority provides for developing,
amendi ng, and admi ni s t ering radi ation safety performance standards for
e l ect ronic products .
Sunlamp products are class I medical devices exempt from premarke t
notification requirements (21 CFR 878 . 4635) . These products are intended to
provide u l t raviolet (UV) radiat i on to tan t he s kin . As class I devices ,
sunl amp products are subject t o general cont rols such as registration,
listing, and current good manufacturing pract ices . Sunlamp products are also
subject to the regulations for electronic product radiation control including
par t s 1000 t hrough 1010 and 1040 . 20 (21 CFR parts 1000 t hrough 1010 and 21
CFR 1040 . 20) .
The sunlamp performance standard in 1040 . 20 was ori g i nal ly publ ished in
the Federa l Register of November 9, 1979 (44 FR 65352) . On September 6, 1985
(50 FR 36548) , FDA amended 1040 . 20 and made it appl i cabl e to a l l sunlamp
p roducts manufactured on or after September 8 , 1986 . On August 21 , 1986, FDA
issued a guidance entitled " Policy on Maximum Timer Interval and Exposure
Schedule for Sunlamp Products ." The guidance explained the criteria FDA uses
to evaluate the adequacy of the exposure schedule and the recommended maximum
exposure t ime for sunlamp products . On September 2 , 1986, FDA issued another
guidance ent itled " Policy on Lamp Compatibi l i t y ." The guidance l ist ed the
criteria FDA use s to evaluat e lamp compat i b i l i ty for sunlamp products .
Before proposing any electronic product performance standards , FDA is
required to consult a statutory advisory committee , the Technical Electronic
Product Radi a t ion Safety Standards Commi t t ee ( TEPRSSC) (21 U. S . C.
360kk(f) (1) (A)) . At the September 23 and 24, 1998 , meeting of TEPRSSC, FDA
presented general concepts for amendments to the performance standard for
sunlamp products . The commit tee recommended that FDA pursue development of t he
amendments . FDA intends to present more specific proposals t o amend the
performance s t andard to TEPRSSC prior t o t he publ i cat i on of a proposed rul e
in the Federal Regis t er .
FDA is concerned that inadequate attention is being paid to the recommended
exposure schedule which should be designed to minimize risks for those who
choose to produce and maintain a tan . FDA is fur ther concerned t hat the
warnings f or sunlamp product s are not reachi ng many users of sunlamp product s
and that t he exi s t ing exposure schedul e does not t ake into account t he
var i ations i n indi vi dual human UV sensit ivity. I n order t o update the current
sunlamp product standards , FDA is considering revising 1040 . 20 .
I n addi t i on, sunl amp technology cont i nues t o change . These changes can
a f fec t bot h the intensit y and the spectral characteristi cs of the UV f rom
sunl amps . Because there is no uni f orm grading/rat i ng system, choosing a
replacement lamp can be confusing for tanning bed owners . Owners choosing
replacement lamps must consider lamp compatibility as well as compliance with
FDA ' s performance standard in order to protect users from excessive exposure
to UV .
I n addi t i on t o concerns about t he warni ngs , l abel ing, and exposure
schedule, FDA is aware of new research f indi ngs that suggest a stronger
associ a t ion between exposures t o ultravi o l et radiati on and the i ncreased
incidence of skin cancer that has been observed in the U. S . populat ion . Some
of this increase has b een linked to intense, intermi ttent exposures to solar
r a diation, but other research suggests that chronic, less intense exposures to
ultraviolet radiation also contribute to skin cancer . Research has ident ified
the fundamental chemical damage that occurs in the genet ic material of humans
and has l i nked some s kin cancers t o changes in speci f i c genes . These
scientific findi ngs have l ed many in the medical communi ty t o strongly suggest
that consume r s avoi d intense , inte rmittent exposures ( the type that could
produce sunburns ) to ult raviole t radiation, and also minimize o t her UV
e xposures as we ll .
There are o t her de l e t eri ous e f f ect s f rom human e xposure t o UV radi a t i on .
They i nclude bl i s t ering bur ns , ski n eryt he ma, phot oagi ng, and
photoallergi c/photosensitive drug int eractions . UV radiation may induce damage
in the cornea, lens , and retina of the eye , which in ext r eme cases lea d s to
permanent loss of vision . UV exposure is immunosup p ressive , and can have an
impact on the development of many d iseases .
Some research has l inked s kin cancer to e xposures t o sunl amp products , and
some research has even sugges t ed an associ a tion be t wee n t he use o f sunlamps
and mal i gnant me lanoma . Thi s associ a t i on i s not de f i ni t i ve . FDA solic i t s
comments and informat i on as to whether a warning about possible melanoma
induction should be pa rt of s unlamp l abel s . To provide user s with s uffici e nt
information for the safe use of these devices at tanning salons and for home
sunlamp product s , FDA s eeks comments and informat ion on suggested change s to
the current sunlamp labels .
Aft er c onsi de r i ng t he risks , some consumers may s t i l l choose t o t an, e i t her
by e xposure t o t he sun or by use of sunl amp product s . Those consumers who use
s unlamp product s should obtain their tan with t he least amount of risk from
s unburn and eye damage . Therefore, FDA seeks a dvice on a recomme nded exposure
schedule which would minimize the risks of a dve r se effects while still
producing and maintaining a t an .
I I . Revi s i ons Under Considerat ion
FDA believe s t hat ame ndme nt of t he current pe r f ormance s t andard i s
necessary to keep pace with changes in technology and advances in research
rel a t e d to the use of sunlamp prod uct s . The following di scussion i s inte nded
to describe the need for the revi s ion and FDA ' s p roposed approac h . Comments
received from thi s a d vance not ice of proposed rulemaking (ANPRM) will be used
to devel op any proposed amendments . Any proposed regul a t ory changes or
s t andar ds amendments wi ll be i ncluded in a f ut ure proposed rul e . FDA i s
sol i c i t i ng comme nt s on al l aspects of t his ANPRM, and specifical ly reque s t s
comments on t he following proposed amendments :
1 . FDA i s considering revising a nd updat ing the current s unlamp p roduc t
performance s t andard ( 1040 . 20) and harmoni z i ng i t wi th t he I nt ernat i onal
El ect rot echni cal Commi t t e e St andard 335-2-27 f o r UV and infrared e mi t t ing
appliances . Aft er consulting with int ernational standards organizations and
evalua t ion of t he current scientific knowledge , FDA intends to develop a
recommende d exposure schedule which will become part of the directions for use
of the sunlamp product . As part of the development process , FDA intends to
review the material on effects of UVA and UVB on skin, the effects of UV
exposure on melanoma induction, and the use of photobiological action spectra
as a basis for risk assessment in health protection and product safety
discussed at the American Society for Photobiology and European Society for
Photobiology Joint Workshop on UV and Melanoma , Snowbird, Utah , July 11
[*6290] through 15, 1998; the International Symposium and Workshop on
Measurements of Optical Radiation Hazards , at the National Institute for
Standards and Technology , Gaithersburg , MD , September 1 through 3 , 1998 ; and
(3) the Research Workshop on Risks and Benefits of Exposure to Ultraviolet
Radiation and Tanning , at the National Institutes of Health, Bethesda, MD ,
September 16 through 18, 1998 . The proceedings of these meet ings describe
current r esearch findings that show a stronger corre l a tion betwee n UV exposure
and s kin cancer , photoaging , and photoimmunological e ffect s .
2 . FDA is considering revising and updating its August 21 , 1986, guidance
on the determination of the maximum timer interval and recommended exposure
schedule for sunlamp products entitled, " Policy on Maximum Timer Interval and
Exposure Schedul e for Sunl amp Products ." FDA i s concerned that i nadequat e
a t t ent ion is bei ng pai d to current recommended exposure schedules and that
current guidance may allow higher exposures than are necessary t o produce and
maint ain a tan, and it does not incorporate the differences in individual
human sensitivity to UV exposure . FDA intends to update this guidance after
reviewing and evaluating material presented at the meetings listed previously
and other available information . FDA is further considering incorporating the
previous guidance into the sunlamp product performance standard because it
beli eves such incorporat ion woul d result i n a more comprehensi ve regul a t ory
s t andard wit h a l l rel e vant i nformat i on for compl iance in t he standard.
3 . FDA is considering adding a provision clarifying that manufacturing
includes the modification of a sunlamp product , previously certified under
1010 . 2 , by any person engaged in t he business o f manuf acturi ng, assembl i ng or
modi fying sunl amp products i f the modi f i cat i on affects any aspect o f t he
product ' s performance , information or intended function for which 1040 . 20
has an applicable requirement . This addition would clarify t hat sunlamp
products are bei ng regul a t ed l i ke o t her products regul a t ed under 1010 . 2 . FDA
is also considering requiring the manufacturer who performs such modification
to recertify and re- identify the product in accordance with the p rovisions of
1010 . 2 and 1010 . 3 . This potent i a l amendment i s intended to c l ari f y the
respons i b i l i t i es of f i rms and indi vi dual s who are in t he business of
instal l i ng ult ravi o l et l amps and new timers wi th different performance
characteristics than the original lamps and t imers in previously cert ified
products .
4 . FDA is concerned t hat the current warning label is not read by many
tanning salon patrons because it is too long and detailed . Therefore , FDA is
considering updating the warning statement required by 1040 . 20(d) (1 ) (i ) to
simplify the wording and to highlight the risk of skin cancers . In order to
update the warning statements , FDA intends to review and e va luate
epidemiological and mechanistic information on uv exposure- related skin
cancers , i ncludi ng possi b l y fatal cutaneous mal i gnant melanoma . In devel oping
i t s speci f ic proposal for this i tem, FDA wi l l be reviewi ng t he mat erial
presented a t t he meet i ngs c i ted previously and o t her avai l able i nf ormat i on .
5 . FDA is considering requiring the reproduction of the text of the warning
s t a t ement speci f ied in 1040 . 20(d) (1 1 ( i) in cat a l ogs , speci f i cat i on sheet s ,
and brochures pert a i ni ng t o sunl amp products . FDA is concerned t hat consumers
who purchase sunlamp product s through catalog mai l order or through catalogs
on electronic media may not receive information about the associated hazards
and risks until the products are delivered to their homes and unpacked .
6 . To simplify appropriate lamp replacement , FDA is considering the
development of a biological efficacy rating scale for ultraviolet lamps
intended f or use i n sunl amp products . Lamp t echnol ogy cont inues to evolve ,
a f fect ing the levels of UV exposure , t he spect ral characteri s t ics and,
t herefore, t he biologi cal e f f i cacy of ul traviolet lamp radiat i on . At present,
a label that specifies the type of lamps suitable for replacement in the
product is required on sunlamp products and in the user instructions . As new
l amps and new l amp manufacturers enter the marketplace , while other
manufacturers abandon the marketplace , it is increasingly cumbersome to keep
track of individual lamp designations which are compatible with the product
and compl i ant wi th t he standard . I n order to simpl i f y the process , especial l y
for indust ry and State regul a t ors , FDA i s considering a uni f orm grading/rat i ng
syst em.
III . Comments
Interested persons may, on or before May 10, 1999, submit to the Dockets
Management Branch (address above) writ ten comments regarding t h is ANPRM. Two
copi es of any comments are to be submi t t ed, except that indi v i dual s may submi t
one copy . Comment s are t o be i dentifi e d wi t h the docke t number found i n
bracke t s in t he heading of this document . Received comments may be seen in the
office above between 9 a . m. and 4 p . m., Monday through Friday . Thi s ANPRM is
i ssued under section 5 31 e t seq . of the Fe de r a l Food , Drug, and Cosmet i c Act
(21 U.S.C. 360hh et seq .) and under authority o f t he Commi ssioner o f Food and
Drugs .
Dated : Februa ry 2 , 1999 .
William K. Hubbard,
Associ a t e Commiss i oner for Policy Coordi nat i on .
[FR Doc . 99-3109 Fi l ed 2-8-99; 8 : 45 am]
BILLING CODE 4160- 01- F
DATE : SEPTEMBER 10, 2008
CLIENT : TANNING
LIBRARY : HEALTH
FILE : FE DREG
YOUR SEARCH REQUEST IS :
TANNING
AND ULTRAVIOLET
NUMBER OF DOCUMENTS FOUND WITH YOUR REQUEST THROUGH :
LEVEL 1. .. 645 LEVEL 2 ... 71
FEDERAL REGISTER
Vol. 66, No. 143
Rules and Regulations
DEPARTMENT OF HEALTH AND HUMAN SERVICES (HHS)
Food and Drug Administration (FDA)
21 CFR Parts 862, 864, 866, 868, 870, 872, 874, 876, 878, 880, 882, 884, 886,888, 890, and 892
[Docket No. 01N-0073]
Medical Devices; Exemption From Premarket Notification Requirements; Class !Devices; Technical Amendment
Part II
66 FR 38786
DATE: Wednesday, July 25,2001
ACTION: Final rule; technical amendment.
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To view a specific page, transmit p* and the page number, e.g. p* 1
[*38786]
SUMMARY: The Food and Drug Administration {FDA) is amending the language in its medical device
classification regulations for class l devices for consistency, to include in sections where it was not present, a
specific reference to the limitations on exemptions from premarket notification requirements for each generic device
classified. The specific reference language was included when some class I generic devices were first exempted
under provisions of the Food and Drug Administration Modernization Act of 1997 (FDAMA). These amendments
will provide the same reference for devices that were exempted before that time. The language is intended to
conveniently provide the reference, and make the sections clear and easy to read. The status of the devices is not
being changed.
DATES: This rule is effective July 25, 200 I.
FOR FURTHER INFORMATION CONTACT: HeatherS. Rosecrans, Center for Devices and Radiological
Health (HFZ-404), 9200 Corporate Blvd., Rockville, MD 20850,301-594-1190.
SUPPLEMENTARY INFORMATION:
I. Background
Under section 513 of the act (21 U.S. C. 360c), FDA must classify devices into one of three regulatory classes:
Class I, class II, or class III. FDA classification of a device is determined by the amount of
regulation necessary to provide a reasonable assurance of safety and effectiveness.
Under the 1976 amendments (Public Law 94-295), as amended by the SMDA (Public Law 101-629), clevicet are
to lite clauifiecl into clast I <eneral control$) if there ltlnfor111atlon thowln that the neral
control$ of the act are tufflclent to enture tafet" ancleHedlueneu; into class II (special controls), if
general controls, by themselves, are insufficient to provide reasonable assurance of safety and effectiveness, but
there is sufficient inf01mation to establish special controls to provide such assurance; and into class ill (premarket
approval), if there is insufficient infonnation to support classifying a device into class I or class II and the device is a
life-sustaining or life-supporting device, or is for a use which is of substantial importance in preventing impairment
of human health, or presents a potential unreasonable risk of illness or injury.
Most generic types of devices that were on the market before the date of the 1976 amendments (May 28, 1976)
(generally referred to as preamendments devices) have been classified by FDA under the procedures set forth in
section 513(c) and (d) of the act through the issuance of classification regulations into one of these three regulatory
classes. Devices introduced into interstate commerce for the first time on or after May 28, I 976 (generally referred to
as postamendments devices) are classified through the premarket notification process under section 510(k) of the act
(21 U.S. C. 360(k)). Section 510(k) of the act and the implementing regulations in 21 CFR part 807 require persons
who intend to market a new device to submit a premarket notification report (51 O(k)) containing information that
allows FDA to determine whether the new device is substantially equivalent within the meaning of section 513(i) of
the act to a legally marketed device that does not require premarket approval. Unless exempted from premarket
notification requirements, persons may not market a new device under section 51 O(k) of the act, unless they receive a
substantial equivalence order from FDA or an order reclassifying the device into class I or class IT, under section
513(f) of the act.
On November21, 1997, the President signed FDAMA into law (Public Law 105-115). Section 206 of FDAMA, in
part, added a new section 51 0(1) to the act. New section 51 0(1) of the act became effective
February 19, 1998. It provides that a class I device is exempt from the premarket
notification requirements under section 51 O(k) of the act, unless the device is
intended for a use that is of substantial importance in preventing impairment of
human health or it presents a potential unreasonable risk of illness or injury.
To implement this provision, FDA evaluated all class I devices to determine which
device types should become exempt under new provision 51 0(1) of the act and which
device types should remain subject to the requirements of 510(k) of the act. FDA then
amended its classification regulations, in part, by publishing in the Federal Register of February 2, 1998 (63 FR
5387), a list of certain class I devices that would become exempt from 510(k) requirements on February 19, 1998,
subject, however to the limitations found in each classification regulation section (e.g., 2/ CFR 862.9, 864.9, etc.),
63 FR 5387, February 2, 1998. The limitations language of each classification states that if a class I or IT devices is
intended for a use different from that of a legally marketed device in that generic type, or if the modified device
operates using a different fundamental scientific technology than that of a legally marketed device in that generic
type, a new 51 O(k) submission and clearance is required. The limitations language also lists specific intended uses
for in vitro diagnostics devices that would preclude an exemption from the requirements of 51 O(k). FDA issued a
proposed rule in the Federal Register of November 12, 1998 (63 FR 63222), to designate class I devices that are
exempt from the premarket notification requirements, subj ect to certain limitations, and to designate class I devices
that remain subject to premarket notification requirements under the new statutory criteria. The designations of these
devices were codified by a final rule in the Federal Register of January 14, 2000 (65 FR 2296).
As published in the January 14, 2000, Federal Register, the amendments state, in part, that the limitations in each
classification regulation apply to the premarket notification exemptions for each generic device classified in each
section. In addition to mentioning the limitations generally in each classification regulation, FDA noted in the
Federal Register of January 14, 2000, publication that, for clarity and convenience, the classification section for each
generic device newly exempted under section 51 0(1) of the act specifically states that the exemptions are subject to
limitations. The agency fm1her noted that for individual device classification sections that had been codified
previously as exempt from premarket notification requirements, it would add the same subject-to-limitations
language in the future. These amendments now add that language. For example, with this regulation, 21 CFR
862.1190 states that the copper test system "is exempt from the premarket notification procedures in subpart E of
part 807 of this chapter subject to the limitations in 862.9. " (Emphasis added.) FDA is adding this specific
reference to the limitations for [*38787] consistency, clarity, and convenience. The status of the devices is not
changing.
This document is published as a final rule with the effective date shown under the DATES section above. FDA has
already established by regulation that exemptions from premarket notification are subject to certain limitations (e.g.,
21 CFR862.9). This rule merely cross-references, for clarity and convenience, in individual classification regulations
the sections that establish these limitations. FDA, therefore, has determined that this final rule has no substantive
impact on the public. FDA, therefore, for good cause, finds under 5 U.S. C. 553(b)(3)(B) and (d)(3) that notice and
public comment are unnecessary and that this rule may take effect upon publication.
IT. Environmental Impact
The agency has determined under 21 CFR 25.30(h) that this action is of a type that does not individually or
cumulatively have a significant effect on the human environment. Therefore, neither an environmental assessment
nor an environmental impact statement is required.
III. Analysis oflmpacts
FDA has examined the impact of the rule under Executive Order 12866 and the Regulatory Flexibility Act (5
U.S. C. 601-612) (as amended by subtitleD of the Small Business Regulatory Fairness Act of 1996 (Public Law 104-
121)), and the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive Order 12866 directs agencies
to assess all costs and benefits of available regulatory alternatives and, when regulation is necessary, to select
regulatory approaches that maximize net benefits (including potential economic, environmental, public health and
safety, and other advantages; distributive impacts; and equity). The agency believes that this final rule is consistent
with the regulatory philosophy and principles identified in the Executive order. In addition, this rule is not a
significant regulatory action as defined by the Executive order and so is not subject to review under the Executive
order.
The Regulatory Flexibility Act requires agencies to analyze regulatory options that would minimize any significant
impact of a rule on small entities. Because this rule does not change the status quo for these devices, the agency
certifies that this final rule will not have a significant economic impact on a substantial number of small entities.
Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires that agencies prepare a written statement of
anticipated costs and benefits before proposing any rule that may result in an expenditure by State, local, and tribal
governments, in the aggregate, or by the private sector, of $100 million in any one year (adjusted annually for
inflation). The Unfunded Mandates Refonn Act does not require FDA to prepare a statement of costs and benefits
for the final rule, because the final rule is not expected to result in any 1-year expenditure that would exceed $100
million.
IV. Paperwork Reduction Act of 1995
This final rule contains no collections of information. Therefore, clearance by the Office of Management and
Budget under the Paperwork Reduction Act of 1995 is not required.
List of Subjects
21 CFR Parts 862, 866, 868, 870, 872, 874, 876, 878, 880, 882, 884, 888, and 890
Medical devices.
21 CFR Part 864
Biologics, Blood, Laboratories, Medical devices, Packaging and containers.
21 CFR Part 886
* * * * *
******
282. Section 878.4635 is amended by revising paragraph (b) to read as follows:
878.4635 - Ultraviolet lamp for tanning.
* * * * *
(b) Classification. Class I (general controls). The device is exempt from the
premarket notification procedures in subpart E of part 807 of this chapter, subject to
the limitations in 878.9.
283. Section 878.4660 is amended by revising paragraph (b) to read as follows:
*******
FEDERAL REGISTER
Vol. 62, No. 111
Notices
DEPARTMENT OF HEALTH AND HUMAN SERVICES (HHS)
Centers for Disease Control (CDC)
[Program Announcement 775]
Primary Prevention Skin Cancer Strategies for Children, Parents, andCaregivers
62 FR 31604
DATE: Tuesday, June 10, 1997
To view the next page, type .np* TRANSMIT.
To view a specific page, transmit p* and the page number, e.g. p* 1
[*31604]
Introduction
The Centers for Disease Control and Prevention (CDC) announces the availability of fiscal year (FY) 1997 funds
for cooperative agreement projects for ptimary prevention of skin cancer, and to build a national primary prevention
effort that targets children (aged 0-13), parents, and caregivers. Caregivers are defined as those individuals who
spend a significant number of consecutive hours with a child or children on a daily basis, i.e., grandparents, day-care
workers, teachers, foster parents, etc. Project activities will be developed to complement previous and ongoing
efforts of the National Skin Cancer Prevention Education Program (NSCPEP) and focus on two program options.
Applicants may choose one or both of the options. The strategies or activities proposed for each option chosen must
be clearly identified and stand alone, and applications must include separate narratives and budgets for each option
selected.
Applicants not adhering to this requirement will be disqualified.
Option One: Develop and conduct a skin cancer primary prevention intervention.
Option Two: Develop partnerships, coalitions, or interest groups with the lay, professional, and scientific
community that supplement and support the primary prevention efforts of the NSCPEP.
CDC is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000,"
a national activity to reduce morbidity and mortality and to improve the quality of life. This announcement is related
to the priority area of Cancer. (For ordering a copy of "Healthy People 2000", see the section "Where To Obtain
Additional Information.")
Authority
This program is authorized under section 317(k)(2) of the Public Health Service Act, as amended (42 U.S. C.
247b(k)(2)). Applicable program regulations are found in 42 CFR part 5lb-Project Grants for Preventive Health
Services.
Smoke-Free Workplace
CDC strongly encourages all grant recipients to provide a smoke-free workplace and to promote the non-use of all
tobacco products, and Pub. L. 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities that
receive Federal funds in which education, library, day care, health care, and early childhood development services
are provided to children.
Eligible Applicants
Eligible applicants are public and private not-for-profit organizations, governments, and their agencies. Thus,
universities, colleges, research institutions, other not-for-profit public and private organizations, State and local
governments or their bona fide agents, federally recognized Indian tribal governments, Indian tribes or Indian tribal
organizations, and small, minority-and/or women-owned not-for-profit businesses are eligible to apply.
Note: Organizations described in section 50l(c)(4) of the Internal Revenue Code of 1966 that engage in lobbying
are not eligible to receive Federal grant and cooperative agreement funds.
Availability of Funds
Approximately $800,000 is available in FY 1997 to fund approximately four awards. A minimum of one award
will be made for each of the Options. The average award will be $200,000, with awards ranging from approximately
$150,000 to $250,000. It is expected that the awards will begin on or about September 30, 1997, and will be for a 12-
month budget period within a project period of up to 3 years. Funding estimates may vary and are subject to change.
Continuation awards within the project period will be made on the basis of satisfactory progress and the
availability of funds.
Use of Funds
Restrictions on Lobbying
Applicants should be aware of resttictions on the use of HHS funds for lobbying of Federal or State legislative
bodies. Under the provisions of 31 U.S. C. 1352 (which has been in effect since December 23, 1989), recipients (and
their subtier contractors) are prohibited from using appropriated Federal funds (other than profits from a Federal
contract) for lobbying Congress or any Federal agency in connection with the award of a particular contract, grant,
cooperative agreement, or loan. This includes grants/cooperative agreements that, in whole or in part, involve
conferences for which Federal funds cannot be used directly or indirectly to encourage participants to lobby or to
instruct participants on how to lobby.
In addition, the FY 1997 HHS Appropriations Act, which became effective October I, 1996, expressly prohibits
the use of 1997 appropriated funds for indirect or "grass roots" lobbying efforts that are designed to support or defeat
legislation pending before State legislatures. This new law, Section 503 of Public Law 104-208, provides as follows:
Section 503(a) No part of any appropriation contained in this Act shall be used, other than for normal and
recognized executive-legislative relationships, for publicity or propaganda purposes, for the preparation, distribution,
or use of any kit, pamphlet, booklet, publication, radio, television, or video presentation designed to support or
defeat legislation pending before the Congress,* **except in presentation to the Congress or any State legislative
body itself.
(b) No part of any appropriation contained in this Act shall be used to pay the salary or expenses of any grant or
contract recipient, or agent acting for such recipient, related to any activity designed to influence legislation or
appropriations pending before the Congress or any State legislature.
Department of Labor, Health and Human Services, and Education, and Related Agencies Approptiations Act,
1997, as enacted by the Omnibus Consolidated Appropriations Act, 1997, Division A, Title I, section !Ol(e), Public
Law I 04-208 (September 30, 1996).
Background
Skin cancer is the most common form of cancer in the United States, which accounts for more than one million
new cases annually or roughly one third of all new cancer cases. Basal and squamous cell skin cancers are the most
common types of skin cancer and tend to have a low mortality but high morbidity that may result in disfigurement
and disability. Melanoma has a lower incidence, but a higher mortality rate among the skin cancers. The American
Cancer Society estimates that in I 997, 40,300 persons will be diagnosed with melanoma of the skin and 7,300 will
die from the disease. There will be a projected total of 9,490 deaths, 2,100 resulting from basal cell, squamous cell,
and a small proportion of more rare skin cancers. From 1973-1992, the overall percentage increase in the rate of
death of melanoma (34.1%) was the third highest of all cancers. Incidence rates are over 10 times higher among
whites than among blacks (11.7 per 100,000 v. 0.8 per 100,000 for the period 1985-1989). Mortality from cutaneous
melanoma has increased, [*31605] although less rapidly than the incidence. Survival has improved partly because of
an increase in the proportion of cases diagnosed at the localized stage.
Unprotected exposure to ultraviolet radiation, from the sun or nonsolar sources
such as tanning beds, is strongly associated with skin cancer. Melanoma appears to
have a strong association with early life sun exposure and sunburns. Because of the
apparent link between severe sunburns during childhood and increased risk of
melanoma later in life, special efforts should be made to protect children from the
sun. Basal cell cancer and melanoma appear to be occurring at earlier ages, which
implies the early initiation of activities that significantly increase sun exposure
among children.
There are some predisposing risk factors that appear to heighten the propensity for the development of skin cancer
such as the presence or family history of skin cancer; large mole count; fair or light colored complexion, hair and
eyes; and skin that readily burns from sun exposure.
Currently, it is recommended that people of all ages, and especially those with light complexions, limit sun
exposure. Parents and caregivers should limit sun exposure for infants and children. Childhood education is
considered a priority target for prevention because children receive an estimated 70-80 percent of lifetime sun
exposure before the age of 18; excessive sun exposure early in life appears to increase the risk of the subsequent
development of skin cancer later in life, and beneficial behavior patterns established during early childhood often
persist throughout life. Children are particularly at risk for sun exposure and have the greatest lifetime potential to
benefit from positive sun protection habits. Strategies should identify discrete actions children, parents, and
caregivers can take to assure adequate protection from the sun.
Since 1994, CDC has been developing and implementing the NSCPEP program. Related projects funded by CDC
include: development and evaluation of skin cancer primary prevention education strategies; media campaigns with
resultant widespread media dissemination; national skin cancer prevention education agenda-setting meetings;
development of partnerships; development of educational brochures with other agencies and organizations, and
development of guidelines for skin cancer prevention in the school and community. In the fall of 1996, CDC co-
sponsored and participated in a workshop related to basal cell and squamous cell skin cancers, spear-headed by the
National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health. Workshop
deliberations affirmed the need to develop strategies aimed at the protection of children from over exposure to the
sun and the recommendations reflected this. The previously mentioned activities have provided guidance and focus
to CDC's advances in skin cancer prevention. As a result, CDC will continue to focus efforts on primary prevention
strategies that support the initiation, growth, and maintenance of the NSCPEP, partnerships with national
professional organizations, agencies, institutions, and the media.
Purpose
This program will assist in developing and building upon efforts that are consistent with the NSCPEP. The primary
goal of this program is to develop, conduct, and evaluate strategies that effectively reach children, parents, and
caregivers, and are aimed at reducing skin cancer through the adoption of preventive behaviors and the institution of
sun protection measures. These measures may include environmental interventions, such as physical/structural
modifications or incentives. Such strategies could include providing physical structures and accompanying
incentives to seek shade, and requiring the use of hats, protective clothing, etc., when outside or altered times for
outdoor activities.
Program Requirements
In conducting activities to achieve the purpose of this program, the recipient will be responsible for the activities
under A. (Recipient Activities) and CDC will be responsible for the activities under B. (CDC Activities).
A. Recipient Activities
Option One: Develop and conduct a skin cancer primary prevention intervention.
I. Seek input from persons in the targeted population, representative interest groups, and persons who can
complement activities and provide expertise such as medical, behavioral, and public health perspectives.
2. Inventory resources needed to develop, conduct, and evaluate the intervention, such as hardware, software,
skills, capabilities, and material and logistic resources, e.g. training materials, transportation, etc.
3. Develop the intervention.
4. Develop procedures and tools for collecting pre-intervention data, intervention process data, and post
intervention data.
5. Create a marketing plan. Include testing of the plan to ensure that adequate numbers of the targeted population
are informed and have the opportunity to participate.
6. Pilot test the intervention among a representative sample of the targeted population.
7. Conduct the intervention in a defined targeted population, taking into account modifications and adjustments
identified during the pilot test.
8. Analyze and evaluate the results of the intervention using appropriate qualitative or quantitative methods.
Include an assessment of the fidelity of the methodology and protocol, and a description of results with respect to
awareness, knowledge, and to the degree possible, behavioral change atttibuted to the intervention in the targeted
population.
9. Participate in conferences, workshops, and meetings convened by CDC.
Option Two: Develop partnerships, coalitions, or interest groups with the lay, professional, and scientific
community that supplement and support the primary prevention efforts of the NSCPEP.
1. Define and provide justification for the scope of the proposed partnerships, coalition(s), or interest group(s). The
scope can be a diverse group of interested agencies and organizations, including public health; public and private
education agencies; voluntary organizations; advocacy groups; not-for-profit and for profit organizations, etc., or a
more narrowly defined group of interested agencies and organizations that has as their constituent base the
populations for which this program is intended, for example, children and youth organizations; schools; media and
private sector partners; parks and recreation organizations; U.S. sport and athletic organizations, parent
organizations, etc. The magnitude of reach should describe the level at which the activities will occur (local, State,
regional, or national).
2. Develop the purpose, mission, objectives, and expected outcomes of the partnerships, coalition(s), or interest
group(s).
3. Develop criteria for selecting members based on #2, include length of the term and ways to optimize member
involvement and buy in.
4. Define the level of involvement and expected contributions of members. Address issues related to organizational
structure and function; composition of subcommittees and ad hoc committees; decision making processes, etc.
[*31606]
5. Identify ways to enhance process efforts, such as building infrastructure, facilitating group process and
communication, and planning and attending to meeting logistics.
6. Establish an initial agenda for action and facilitate group process to develop a purpose, short-and long-term
goals, and activities.
7. Develop a strategy to sustain partnerships, coalition(s), or interest group(s).
8. Describe plans for integrating efforts and activities into ongoing national efforts.
9. Develop a mechanism for monitoring and reporting coalition activities and accomplishments. This may include,
but is not limited to, meeting minutes, attendance logs, operational and procedural manuals, etc.
10. Participate in conferences, workshops, and meeti ngs convened by CDC.
B. CDC Activities
1. Provide scientific and programmatic technical assistance.
2. Participate with and assist recipient in identifying appropriate agencies and organizations that will enhance
project activities.
3. Collaborate with recipients to develop, implement, evaluate, and disseminate project activities designed to
improve and change the knowledge, attitude, and impact on behaviors of the targeted groups.
4. Monitor the recipient's performance of project activities, attainment of project objectives, and compliance with
other CDC requirements.
5. Provide periodic updates about skin cancer prevention public knowledge, attitudes, and practices, and scientific
data when available.
6. Assist with the design and conduct of the evaluation plan, including project outcomes and process measures, and
modifications, as deemed necessary.
7. Coordinate dissemination of recipients' experiences and results through grantee meetings, workshops, and
conferences with other CDC recipients, other NSCPEP projects, and CDC.
8. Assist recipients with dissemination of project results in the public domain, through venues such as professional
publications, presentations at conferences, etc.
Technical Reporting Requirements
Semi-annual progress reports are required and must be submitted no later than 30 days after each semi-annual
reporting period. The semi-annual progress reports must summarize the following: (I) A comparison of actual
accomplishments to the goals and objectives established for the reporting period; (2) the reasons for slippage if
established goals were not met; and (3) other pertinent infonnation, including, when appropriate, analysis and
explanation of unexpectedly high costs for perfonnance.
An annual financial status report must be submitted no later than 90 days after the end of each budget period. Final
financial and performance reports are required no later than 90 days after the end of the project period. All reports
must be submitted to the Grants Management Branch, Procurement and Grants Office, CDC.
Application Content
All applicants must develop their applications in accordance with PHS Form 5161- 1 (Revised 7/92, OMB Number
0937-0189), information contained in this program announcement, and the instructions outlined below. Applicants
are required to submit an original and two copies of the application. Pages must be clearly numbered, and a complete
index to the application and its appendixes must be included. Begin each separate section on a new page. The
original and each copy of the application must be submitted unstapled and unbound. All materials must be
typewtitten, single-spaced, with unreduced type on 8 112 by 11" paper, with at least 1" margins, headers and footers,
and ptinted on one side only.
Appendixes should be of a reasonable length; only include documents necessary to support the application, such as
Letters of Support and examples of relevant work, as requested.
Applicants should discuss technical, programmatic, and public health expertise they can offer in the development
of national skin cancer prevention efforts and in participation in national meetings and on committees and task
forces. An evaluation plan should be included with the application.
Applicants may elect to submit proposals that address one or both of the options. Each option must be treated as a
separate submission or application and the application(s) should not exceed 30 pages, excluding appendixes.
Option One: Develop and conduct a skin cancer primary prevention intervention.
Option Two: Develop partnerships, coalitions, or interest groups with the lay, professional, and scientific
community that supplement and support the primary prevention efforts of the NSCPEP.
A. Executive Summary
Provide a clear, concise, one-page summary of: (J) The capabilities and experience in conducting activities related
to the Option selected. Include any activities conducted in skin cancer prevention; (2) the major objectives of the
proposed project; (3) roles and responsibilities of proposed project personnel, including collaborators; and (4) the
estimated total cost of the project, including the total funds requested.
B. Demonstrated Capabilities
Provide evidence, based on previous projects, of the ability to:
Option One: Develop and conduct a skin cancer primary prevention intervention.
1. Describe examples of previous primary prevention intervention work, including those in skin cancer prevention
or in other health areas. Discuss organization capability, scope, magnitude of reach (local, State, regional, national),
targeted population, process and evaluation methodology, and desctiption of the outcomes and efficacy.
2. Include evidence of adequate resources to develop, conduct and evaluate interventions, such as staff expertise,
facilities, hardware, and software. Describe the capabilities available to obtain additional resources when
appropriate.
3. Include evidence of direct work with children, parents, and caregivers, and/or evidence of collaborative efforts
on projects with interest groups and organizations, representing children, parents, and caregivers, that have
conducted primary prevention interventions, including those in skin cancer prevention or in other health areas.
Option Two: Develop partnerships, coalitions, or interest groups with the lay, professional, and scientific
community that supplement and support the current efforts of the primary prevention educational activities of the
NSCPEP.
1. Describe previous experiences and provide examples of development or substantive participation and sustain
ability of previous partnerships, coalition(s), or interest group(s). Include names or types of members, scope,
magnitude of reach (local, State, regional, national), process and evaluation methodology, and a description of
outcomes and efficacy.
2. Describe the organizational role and processes employed to ensure adequate [*31607] resources to develop,
implement, evaluate, and sustain partnerships, coalition(s), or interest group(s).
3. Describe and include evidence of past or current experience and participation in partnerships, coalition(s), or
interest group(s) that have children, parents, or caregivers as constituents, and that have conducted prevention
activities.
4. Include final reports, proceedings, materials developed, or a list of accomplishments resulting from group
activities in the appendix.
C. Project Objectives
Submit overall project objectives that are specific, measurable, realistic, and time-phased. Activities during year
01 through year 03 should be related and build on previous work. This should be reflected in the overall project
objectives. The objectives and activities related to year 01 should be described in detail. Year 02 and 03 objectives
and activities should be briefly described. End-of-year and end-of-project expected outcomes should be included.
D. Operational Plan
Describe the operational plan for achieving each of the objectives established in section C. Provide a concise
description of each major activity, and how it will be carried out. Include proposed collaborative efforts. Include
relevance to the National Skin Cancer Prevention Education Program efforts. The plan must have a timeline for
completion of each major activity. The year 0 I timeline must include specific process steps and include CDC review
and approval.
Letters of support that specify the precise nature of proposed collaboration, and the products, services, capabilities,
or other activities that will be provided through the collaboration should be included in the appendix.
Specifically for the Option selected, the Operational Plan should include the following:
Option One: Develop and conduct a skin cancer primary prevention intervention.
1. Describe and provide a rationale for the proposed intervention. Include specific process steps that will be
undertaken to accomplish the proposed project. These steps should include, but are not limited to:
(a) The extent of problem; targeted population selection and rationale; baseline data on knowledge, attitudes, and
practices; literature review; incorporation of existing primary prevention or skin cancer prevention eff01ts;
theoretical framework; goals and objectives; development of intervention and marketing plan, including testing of
the intervention, to ensure that adequate numbers of the targeted population are informed and have the opportunity to
participate, and development of data collection tools. Include the availability of resources to be used on this project,
such as skills, capabilities, materials, and facilities.
(b) Plans for the implementation of the intervention, following the pilot or pretesting of the intervention in a
sample population. Include sampling, mechanisms for modification and retesting, and conduct of the intervention in
the population.
(c) The fonnative, outcome, and process measures proposed, and the methodology used to evaluate these
measures.
(d) The expected impact on the efforts of the NSCPEP.
2. Include specific plans to collaborate with key agencies and organizations representing targeted populations,
CDC, other grantee recipients, and current NSCPEP efforts. Include letters of support (in the appendixes) from
agencies and organizations with a substantive role in the proposed activities.
3. Include a detailed timeline for all proposed activities.
4. Include evaluation methodology of the intervention by using appropriate qualitative or quantitative methods.
Include an assessment of the fidelity of the selected methodology and protocol, and a description of proposed results
with respect to awareness, knowledge, and to the degree possible, behavioral change attributed to the intervention in
the targeted population.
Option Two: Develop partnerships, coalitions, or interest groups with the lay, professional, and scientific
commuojty that supplement and support the primary prevention efforts of the NSCPEP.
1. Include the scope of partnerships, coalition(s), or interest group(s). This should include the proposed
composition (diverse versus narrow) and the proposed magnitude of reach (local, State, regional, or national).
2. Include the proposed purpose, objectives, and expected outcomes of the partnerships, coalition(s), or interest
group(s).
3. Include criteria used for selecting members, ways to use and optimize member involvement, plans to sustain
membership and proposed members or types of members. Include in the appendix, Letters of Support from persons
interested and willing to participate.
4. Include process steps used to conduct the meetings; facilitate group process; build group infrastructure;
communi cate with the group before, during, after, and between meetings; and manage and plan for meeting activity
logistics, including travel, meeting space, etc.
5. Include an initial plan for action and methods for facilitating the group to develop the purpose; short- and long-
term goals; and activities of the group.
6. Include a detailed timeline for all proposed activities.
7. Include plans to coordinate with other grantees, and other NSCPEP skin cancer prevention coalitions currently
in progress, and CDC.
E. Project Management
Describe the capabilities, function, time dedication, and qualifications required for each position. Include
collaborators, their qualifications, and reason for their selection.
Specifically for Option selected, Project Management should include the following:
Option One: Provide evidence that a well-balanced team of experts bas been assembled to assure that the
intervention selected will be designed and developed by using necessary sciences. Include behavioral scientists,
evaluation scientists, dermatologists, public health personnel, and the targeted audience in all steps of the process.
Option Two: Provide evidence that a staff person or a consultant has been retained who has expertise in group
process and facilitation, as well as substantive experience in coalition development, management, and evaluation.
Include evidence of strong management, organizational , and human relations skills.
F. Budget
Provide a detailed budget request (using Standard Form 424A "Budget Information") and line-item justification of
all proposed operating expenses consistent with the option selected and the proposed activities. Use the sample
budget included in the application kit as a guide to budget development. Include the folJowing:
1. Travel plans in year 01: Budget two trips to CDC in Atlanta, Georgia, for conferences, workshops, or a reverse
site visit. Plan to travel one or two persons, for one to three days.
2. All proposed contracts must indicate the following: (1) Name of contractor, (2) Method of selection, (3) Period
of performance, (4) Scope of work, (5) Method of accountability, and [*31608] (6) Detailed budget with a
justification for costs.
Evaluation Criteria (Total of 100 Points)
The application will be reviewed and eval uated according to the following criteria:
A. Demonstrated Capabilities (20 Points Each)
The extent to which all items in the application content are addressed for Option selected including:
1. Provides examples of previous work similar to the nature of Option selected. Includes targeted populations,
scope, magnitude of reach (local, State, regional, national), evaluation methodology, and outcomes and efficacy.
2. Provides evidence of adequate resources to develop, conduct, and evaluate activities, such as staff expertise,
working knowledge of Option selected, facilities, logistical support, and hardware and software.
3. Provides evidence of direct work with children, parents and caregivers, or evidence of collaborative efforts on
projects with interest groups and organizations representative of these that have conducted prevention activities.
B. Project Objectives (20 Points)
The extent to which all items in the application content are addressed for Option selected including:
The appropriateness of proposed objectives that are specific, measurable, time-phased, and realistic for year 01
activities, and a brief description of proposed objectives for years 02 and 03, and the extent to which end-of-year,
and end-of-project expected outcomes are described and effect the effort of the National Skin Cancer Prevention
Education Program. Epidemiologic data should be included to support and prioritize the need for a targeted primary
prevention activity in the Option selected.
C. Operational Plan (Option One: 40 Points Total, 25 Points for the General Operational Plan and 15 Points for the
Evaluation Plan; Option Two: 35 Points Total, 25 Points for the General Operational Plan and 10 Points for the
Evaluation Plan)
The extent to which all items in the application content are addressed for Option selected including:
I. Provides evidence of a planning process that includes data and needs assessment, literature review, activity
selection, and selection of the targeted population (Option One), partnerships, coalition(s), or interest group(s)
(Option Two).
2. Provides a cogent, logical, complete description and process steps of activities.
3. Provides goals, project objectives, and expected outcomes.
4. Provides a timeline that includes CDC review and approval at critical decision-making and work-related steps.
5. Provides evidence of resources necessary to successfully address the activities, such as skills, capabilities and
staff, logistical support, and hard and software necessary to carry out Option selected.
6. Provides a plan to market and disseminate activities.
7. Provides an Evaluation Plan that includes the methodology for monit01ing formative process, and outcome
measures. Includes a description of data collection tools; CDC collaboration, review and approval; Human Subjects,
Minorities and Women Research review and other agency review.
D. Project Management (Option One: 20 Points Each; Option Two: 25 Points)
The extent to which all items in the application content are addressed for Option selected including:
Provides a description of the capabilities, function, and qualifications of the proposed staff, staff functions, and
other resources needed to effectively pe1i'orm requested activities in selected Option.
E. Budget (Not Weighted)
The extent to which the applicant provides a detailed budget and justification consistent with the stated objectives
and proposed project activities for Option selected included in the application content and with this program
announcement.
F. Human Subject (Not Weighted)
Whether or not exempt from the Department of Health and Human Services (DHHS) regulations, are procedures
adequate for the protection of human subjects? Recommendations on the adequacy of protections include: (1)
Protections appear adequate and there are no comments to make or concerns to raise; (2) protections appear
adequate, but there are comments regarding the protocol, (3) protections appear inadequate and the Objective
Review Group (ORG) has concerns related to human subjects; or (4) disapproval of the application is recommended
because the research risks are sufficiently serious and protection against the risks are inadequate as to make the
entire application unacceptable.
Noncompeting Continuation Application Content
In compliance with 45 CFR 74.12l(d) and 92.10(b)(4), as applicable, noncompeting continuation applications
submitted within the project period need only include:
A. A brief progress report that describes the accomplishments of the previous budget period.
B. Any new or significantly revised items or information (objectives, scope of activities, operational methods,
evaluation, etc.) not included in the Year 01 application.
C. An annual budget and justification. Existing budget items that are unchanged from the previous budget period
do not need re-justification. Simply list the items in the budget and indicate that they are continuation items.
Supporting justification should be provided where appropriate.
Executive Order 12372 Review
Applications are subject to Intergovernmental Review of Federal Programs as governed by Executive Order (E.O.)
12372. E.O. 12372 sets up a system for State and local government review of proposed Federal assistance
applications. Applicants should contact their State Single Point of Contact (SPOC) as early as possible to alert them
to the prospective applications and receive any necessary instructions on the State process. For proposed projects
serving more than one State, the applicant is advised to contact the SPOC of each affected State. A current list of
SPOCs is included in the application kit. If SPOCs have any State process recommendations on applications
submitted to CDC, they should send them to Sharron P. Orum, Grants Management Officer, Grants Management
Branch, Procurement and Grants Office, Centers for Disease Control and Prevention (CDC), 255 East Paces Ferry
Road, NE., Room 314, Mailstop E-18, Atlanta, GA 30305, no later than 60 days after the application deadline date.
The Program Announcement Number and Program Title should be referenced on the document. The granting agency
does not guarantee to "accommodate or explain" State process recommendations it receives after that date.
Indian tribes are strongly encouraged to request tribal government review of the proposed application. If tribal
governments have any tribal process recommendations on appli cations submitted to CDC, they should forward them
to Sharron P. Orum, Grants Management Officer, Grants Management Branch, Procurement and [*31609] Grants
Office, Centers for Disease Control and Prevention (CDC), 255 East Paces Ferry Road, NE., Room 314, Mailstop E-
18, Atlanta, GA 30305.
This should be done no later than 60 days after the application deadline date. The granting agency does not
guarantee to "accommodate or explain" for tribal process recommendations it receives after that date.
Public Health System Rep011ing Requirements
This program is subj ect to the Public Health System Reporting Requirements. Under these requirements, all
community-based nongovernmental applicants must prepare and submit the items identified below to the head of the
appropriate State ancllor local health agency(s) in the program area(s) that may be impacted by the proposed project
no later than the receipt date of the Federal application. The approptiate State ancllor local health agency is
determined by the applicant. The following information must be provided:
a. A copy of the face page of the application (SF 424).
b. A summary of the project that should be titled "Public Health System Impact Statement" (PHSIS), not exceed
one page, and include the following:
(1) A description of the population to be served;
(2) A summary of the services to be provided; and,
(3) A description of the coordination plans with the appropriate State ancllor local health agencies.
If the State and/or local health official should desire a copy of the entire application, it may be obtained from the
state Single Point of Contact (SPOC) or directly from the applicant.
Catalog of Federal Domestic Assistance Number
The Catalog of Federal Domestic Assistance Number is 93.283.
Other Requirements
Paperwork Reduction Act
Projects that involve the collection of information from 10 or more individuals and funded by the cooperative
agreement will be subject to review by the Office of Management and Budget (OMB) under the Paperwork
Reduction Act.
Human Subjects
If the proposed project involves research on human subjects, the applicant must comply with the Department of
Health and Human Services Regulations, 45 CFR part 46, regarding the protection of human subjects. Assurance
must be provided to demonstrate that the project will be subj ect to initial and continuing review by an appropriate
institutional review committee. The applicant will be responsible for providing assurance in accordance with the
appropriate guidelines and form provided in the application kit.
In addition to other applicable committees, Indian Health Service (IHS) institutional review committees also must
review the project if any component of IHS will be involved or will support the research. If any American Indian
community is involved, its tribal government must also approve that p01tion of the project applicable to it.
Women, Racial, and Ethnic Minorities
It is the policy of the CDC and the Agency for Toxic Substances and Disease Registry (ATSDR) to ensure that
individuals of both sexes and the various racial and ethnic groups will be included in CDC/ATSDR-supported
research projects involving human subjects, whenever feasible and appropriate. Racial and ethnic groups are those
defined in OMB Directive No. 15 and include American Indian, Alaskan Native, Asian, Pacific Islander, Black and
Hispanic. Applicants shall ensure that women, racial and ethnic minority populations are appropriately represented
in applications for research involving human subjects. Where clear and compelling rationale exist that inclusion is
inappropriate or not feasible, this situation must be explained as part of the application. In conducting review for
scientifi c merit, review groups will evaluate proposed plans for inclusion of minoriti es and both sexes as part of the
scientific assessment of scoring.
This policy does not apply to research studies when the investigator cannot control the race, ethnicity and/or sex of
subjects. Further guidance to this policy is contained in the Federal Register, Vol. 60, No. 179, pages 47947-47951,
dated Friday, September 15, 1995.
Application Submission and Deadline
The original and two copies of the application PHS Form 5161-1 (Revised 7/92, OMB Number 0937-0189), must
be submitted to Sharron P. Orum, Grants Management Officer, Grants Management Branch, Procurement and
Grants Office, Centers for Disease Control and Prevention (CDC), 255 East Paces Ferry Road, NE., Room 314,
Mailstop E-18, Atlanta, GA 30305, on or before July 29, 1997.
1. Deadline: Applications shall be considered as meeting the deadline if they are either:
(a) Received on or before the deadline date; or
(b) Sent on or before the deadline date and received in time for submission to the objective review group.
(Applicants must request a legibly dated U.S. Postal Service postmark or obtain a legibly dated receipt from a
commercial carrier or U.S. Postal Service. Private metered postmarks shall not be acceptable as proof of timely
mailing.)
2. Late Applications: Application whi ch do not meet the cri teria in l.(a) or l.(b) above are considered late
applications. Late applications will not be considered in the current competiti on and will be returned to the applicant.
Where To Obtain Additional Information
To receive additional written information, call (404) 332-4561. You will be asked to leave your name, address, and
telephone number. Please refer to Announcement 775. You will receive a complete program description, information
on application procedures and application fonns. If you have questions after reviewing the contents of all the
documents, business management technical assistance may be obtai ned from Glynnis D. Taylor, Grants Management
Specialist, Grants Management Branch, Procurement and Grants Office, Centers for Disease Control and Prevention,
255 East Paces Ferry Road, NE., Room 314, Mailstop E-18, Atlanta, GA 30305, telephone (404) 842-6593, or
Internet or CDC WONDER electronic mail at gldl cdc.gov.
Programmatic technical assistance may be obtained from Barbara A. Bewerse, M.N. , M.P.H., Division of Cancer
Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease
Control and Prevention (CDC), 4770 Buford Highway, NE., Mailstop K-57, Atlanta, GA 30341-3724, telephone
(404) 488-4347, or Internet or CDC WONDER electroni c mail at byb0cdc.gov.
Please refer to Announcement 775 when requesting information and submitting an application.
You may obtain this and other announcements from one of two sites on the actual publication date: CDC's
homepage at http://www.cdc.gov or the Government Printing Office homepage (including free on-line access to the
Federal Register at http://www.access.gpo.gov).
Potential applicants may obtain a copy of "Healthy People 2000" Full [*3161 O]Report, Stock No. 017-001-00474-
0) or "Healthy People 2000" Summary Report, Stock No. 017-00 1-00473-1) referenced in the "Introduction" through
the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325, telephone (202) 512-
1800.
Dated: June 4, 1997.
Joseph R. Carter,
Acting Associate Director for Management and Operations Centers for Disease Control and Prevention (CDC).
[FR Doc. 97-15062 Filed 6-9-97; 8:45am]
Issue Number 7- SPECIAL EDITION Summer2005
The Truth About Tanning:
What You Need to Know to Protect Your Skin
There's no such thing as a safe tan.
Don't mistake the tan you get from hours spent by the
pool or under tanning lamps for a healthy summer glow,
it's actually a sign of sun damage from UV rays and can
~ ~ cause premature aging and skin cancer. But protecting
your skin now can help prevent the side effects caused by
too much sun.
The Inescapable UV Ray
Ultraviolet (UV) radiation is all around us. The most common source is sunlight, which produces three main
types of UV rays: UVA, UVB, and UVC. While UVA and UVB rays are transmitted through the atmosphere, all
UVC and some UVB rays are absorbed by the Earth's ozone layer. Most of the UV rays that reach the Earth's surface
are composed of UVA with a small amount of UVB.
UV light is classified by wavelength. UVB rays have a sh01t wavelength that reaches the outer layer of your skin,
called the epidermis. UVA rays have a longer wavelength that can penetrate and damage the lower layer of your skin,
called the dermis. It's imp01tant to use protection when you're out in the sun
because both UVA and UVB rays can cause sunburn, premature aging, skin cancer,
and damage to the eyes and immune system.
Because UV rays are strongest fromlO a.m. until 4 p.m., it's a good idea to
check the Ultraviolet Index (UVI) before you go outside. UVI is a number from
1-11 that indicates the amount of skin-damaging UV rays reaching the eatth's sur-
face at any point in time. The daily UVI number, listed in the weather section of
most city newspapers, forecasts the amount of UV you'll be exposed to during the
sun's highest point in the sky-usually around noon. The higher the UVI number is,
the more intense the exposure. If your local newspaper doesn't list the UVI for your
area, the Envimnmental Protection Agency (EPA) offers UVI forecasts by ZIP code
at http://www.epa.gov/sunwise/uvindex. html.
When the UVI is 5 or higher, you should always protect yourself from UV
exposure with sunscreen, a brimmed hat, and sunglasses; taking extra care to
reapply sunscreen and seek shade or stay indoors. Also remember that exposure
doesn't come only from above; snow, sand, water, and even concrete reflect UV
In This Issue
The Inescapable UV Ray
Recipe for a Tan
Sunburn
Long-Term Sun Damage
Skin Cancer
Prevention
Sunscreen
In the Salon
Sunless Tanning
Tanning Pills
Learn More
FDA& YOU
rays. In addition, clouds don' t block UVB and you can still get sunburned on a
cloudy day. So it's important to wear sunscreen and protective gear in all types of
weather.
Recipe for a Tan
Page2
DID YOU KNOW?
Direct sun isn't the
only cause of sunburn.
Whether from a day on the beach or hours spent in a tanning salon, the "tan"
color your skin gets after baking under UV rays is a sign of skin damage.
You can get sun-
burned even on a
cloudy day because
UV rays can filter
through the water
droplets that make up
When it's exposed to UV rays your skin produces a pigment called melanin to
protect skin cells from damage. Melanin is the same pigment that already colors
your hair, eyes, and skin. When your skin is exposed to UV rays it produces extra
melanin and may become darker over the next few days.
clouds.
Contrary to what you may have heard, getting a tan doesn't protect your skin from further UV damage.
The extra melanin in tanned skin provides a Sun Protection Factor (SPF) of about 2 to 4; far below the
minimum recommended SPF of 15.
While it's true that sunlight can have the benefit of helping your body produce vitamin D, about 10 to 15
minutes of unprotected sun on your face and bands 2 to 3 times a week provides you with a healthy dose. Too
much sun exposure can lead to sunburn, premature aging, or skin cancer.
Sunburn
Like a tan, a sunburn is a sign of short-term sun damage. Sunburn, also called erythema, is the skin's
natural defense against overexposure to UV rays. When UV rays reach your skin they begin damaging skin
cells in the epidermis. In response, your immune system increases blood flow in the affected areas, making
the skin feel warm and look red. White blood cells, which help protect you from infection and disease, attack
and remove the damaged skin cells. The process of removing the damaged cells can cause the skin to itch and
peel. Meanwhile, the damaged skin cells are releasing chemicals that send messages to your brain. Your
brain translates these messages into a painful burning sensation to let you know you've been sunburned.
Because it can take up to 8 hours for the full effects of sunburn to kick in, you won't realize that you've
been burned right away.
A mild sunburn can be treated with cool baths, over-the-counter
hydrocortisone creams, and aspirin to ease pain and swelling,
according to the American Academy of Dermatology (AAD). A
severe sunburn, usually characterized by a large area of red,
blistered skin with a headache, fever, or chills should be treated
as a medical emergency and examined by a doctor right away.
Studies have shown a link between severe sunburn and
melanoma, the most serious form of skin cancer, so any
sunburn should been taken seriously.
Long-Term Sun Damage
Leathery, wrinkled skin and dark spots are
common earmarks of a lifelong sunbather.
Unfortunately, since these signs of sun damage
don't usually show up until many years later,
you may think you're immune to the long-term
effects of tanning.
FDA& YOU
Everyone, no matter their skin tone, is at risk
for skin damage. There are six skin categories
recognized by the FDA and the AAD. Each is
classified by sensitivity to the sun and typical
skin tone. Check out the table to see which skin
type you are.
The best way to prevent sun damage is to
practice sun safety everyday. That includes wear-
ing sunscreen, a brimmed bat, and sunglasses
every time you go outside. Remember, even if
you can't see it now, the damage done today will
catch up with you later.
Skin Cancer
According to the American Cancer Society,
"Many of the more than 1 million skin cancers
that are expected to be diagnosed in 2005 could
have been prevented by protection from the sun's
rays. "
Skin
Type
I
II
Ill
IV
v
VI
Page3
Sun History Example
Always burns easily, Red-headed, freckles,
never tans, extremely Irish/Scots/Welsh
sun sensitive skin
Always burns easily, Fair-skinned, fair-haired,
tans minimally, very sun blue or green-eyed,
sensitive skin Caucasians
Sometimes burns, tans Average skin
gradually to light brown,
sun sensitive skin
Burns minimally, always Mediterranean-type
tans to moderate brown, Caucasians
minimally sun sensitive
Rarely burns, tans well , Middle Eastern, some
sun insensitive skin Hispanics, some
African-Americans
Never burns, deeply pig- African-Americans
mented, sun insensitive
skin
Experts agree that natural and artificial sunlight, particularly the UV rays, damages the skin. UV rays
cause the obvious short-term damage seen in a sunburn or a tan, as well as the long-term damage that
accumulates with each exposure.
When you tan you greatly increase your risk of developing skin cancer. This is especially true if you
spend time tanning each year because damage to the skin accumulates over time. Unlike skin cancer,
premature aging of the skin will occur in everyone who is repeatedly exposed to the sun over a long time,
although the damage may be less apparent and take longer to show up in people with darker skin.
There are three main types of skin cancer: melanoma, basal cell carcinoma, and squamous cell carcinoma.
Melanoma is the least common but most serious because it's responsible for most of the skin cancer deaths
each year. The other two types, basal cell and squamous cell carcinomas, are often refened to as non-
melanoma skin cancer. Basal cell cancer is the most common skin cancer, followed by squamous cell carcino-
ma, which can also become a killer
A fourth type of growth, actinic or solar keratosis, is also of concern because it can progress into cancer.
It's the most common pre-malignant skin condition, occumng in more than 5 million Americans.
DID YOU KNOW?
Australia has the highest incidence
of skin cancer in the world. To make
it easy for Australians to remember
how to protect their skin,
The Cancer Council Victoria coined
the catchy slogan: Slip! Slop! Slap!
Slip! - Slip on a shirt
Slop! - Slop on SPF 15+ sunscreen
Slap! - Slap on a wide-brim hat
Researchers still aren't sure why some people develop skin cancer
and others don't, but there are some preventive measures you can
take that may reduce your chances of getting skin cancer. While sun-
screens protect against sunburn, they don't necessarily prevent cancer.
If you use sunscreens to spend more time in the sun, your skin could
still be exposed to a high dose of UV, especially the longwave rays.
So it's still a good idea to stay out of the sun at midday, and to protect
yourself with sunglasses, a wide-brim hat, and protective clothing like
a long-sleeved shirt made of thick, light-colored fabric.
Moles or freckles that change shape, color, texture, or get crusty
and bleed could be a sign of skin cancer. Early-stage melanomas
often show up as a light brown to black flat mark that is usually about
FDA& YOU Page 4
Perform A Self Skin Cancer Check
No matter how much time you spend in the sun, you should
protect yourself by checking for signs of skin cancer. Visit
http://www.fda.gov/cdrh/fdaandyou/issue03.html#7 to learn how.
one-quarter inch in size. Any suspect spot
should be checked out by your doctor as soon as
possible. When detected in its earliest stages,
skin cancer is often curable.
For more information on skin cancer, visit
the American Academy of Dermatology's Web
..._ ____________________ ___. site at http://www.aad.org.
Prevention
The best way to protect your skin from the dangerous effects of UV rays is to take simple precautions
every day. Wearing sunscreen, shielding your face and eyes with a wide-brim hat, and sunglasses with a
UV A/UVB rating of 99% or higher, and seeking shade when possible can help decrease your risk.
Clothing can also help protect you from harmful UV in the form of protection you don't need to reapply.
Fabrics can differ greatly in their ability to shield you from UV rays, and natural fibers like cotton offer little
protection when wet.
The ideal sun protective fabrics are lightweight, comfortable, and protect against exposure even when wet.
SPF clothing are available that have thick, tightly woven fabrics with special fibers and dyes to help shield
you from the sun's rays. Remember that light-color fabrics will be cooler in the summer heat.
Certain medications, such as antibiotics, can make you more sensitive to the sun and put you at greater
risk for sunburn. Ask your doctor whether you're taking a medication that could affect your sensitivity to the
sun and what you should do.
Sunscreen
Sunscreen doesn't completely protect you from harmful UV rays, but it can drastically reduce their effects
if used properly. Sunscreen is available in a variety of forms for you to choose from, including sprays, lotions,
gels and wax sticks. Most sunscreens are made of chemicals
that absorb UV radiation. Others create a banier that reflects
the UV radiation away from the skin.
When shopping for sunscreen, chose one that's labeled as
broad-spectrum because it will help protect you from both UVA
and UVB rays. Check the sunscreen label for broad-spectrum
ingredients, such as benzophenones (oxybenzone), cinnamates
(octylmethyl cinnamate and cinoxate), sulisobenzone, salicy-
lates, titanium dioxide, zinc oxide, and avobenzone (Parsol
1789).
All sunscreens are labeled with SPF numbers. The higher
the SPF number, the more protection against sunburn the sun-
screen provides. To get the most protection out of sunscreen
choose one with an SPF of at least 15.
Some sunscreens are labeled as being water-resistant.
These sunscreens stay on the skin longer even if they get wet
from pool water, ocean water, or sweat. But water-resistant
doesn't mean waterproof. Water-resistant sunscreens still need
to be reapplied, so check the label for reapplication times.
Protect Yourself with
These Sun Safety Tips:
* Avoid the sun, or seek shade, from 10 a.m.
to 4 p.m. when the sun's rays are
strongest.
* Apply an SPF 15 or higher sunscreen
* Al low 30 minutes for skin to absorb
sunscreen before going outside.
* Check the label and reapply sunscreen
according to the instructions.
* Wear a wide-brimmed hat.
* Protect eyes with sunglasses that have a
UV/UVB protection of at least 99%.
* Check with your doctor to find out if you're
taking medications that will make you
more sensitive to the sun.
FDA & YOU PageS
The effectiveness of a sunscreen is reduced if it's applied inconectly or if it's washed off, rubbed off, or
sweated off. To make sure you're getting the maximum sunscreen protection, apply an even layer of sunscreen
and reapply it according to the directions.
Sunscreen usually needs about 15-30 minutes to soak in to the skin before you go outside. Read the label
to see how long you should wait. If the label doesn't indicate how long, wait 30 minutes to be safe.
In the Salon
With the convenience offered by a tanning salon, it may be tempting to lie in a tanning bed or sit in front
of a tanning lamp. Fight the urge! Tanning beds and lights are just as dangerous as tanning at the pool or on
the beach. The UVA rays emitted by a tanning lamp or bed are often much more intense than those produced
by the sun. The aging and cancer risks associated with outdoor tanning are the same as tanning in a salon.
For these reasons, the FDA doesn't recommend the use of indoor tanning equipment--EVER
If you insist on using a tanning lamp or bed, follow these steps to reduce the dangers of UV exposure.
Be sure to wear the goggles provided, making sure they fit snugly and aren't cracked.
Start slowly and use short exposure times to build up a tan over time.
Follow manufacturer-recommended exposure times for your skin type. Check the label for exposure times.
Stick to your time limit.
After a tan is developed, tan no more often than twice a week.
The key is to take it slow. If you get the maximum exposure the
first time, you'll probably get burned. And because sunburn takes
several hours to develop you won't realize your skin is burned until
much later.
FDA has a radiation safety perfonnance standard for sunlamp
products. All sunlamp products must have a warning label, an
accurate timer, an emergency stop control, and include an exposure
schedule and protective goggles.
You should NOT use a tanning bed or lamp if:
You sunburn easily and don't tan. Skin that doesn't tan in the
sun probably won't tan with sunlamps either.
You get frequent cold sores. UV radiation may cause them to
appear more frequently.
You're taking medicines that can make you more sensitive to
UV rays. Check with your doctor or pharmacist.
Sunless Tanning
The spray-on glow offered at sunless tanning booths make them a
popular place to maintain a tan year-round. What you may not realize
is that even sunless tanning can have risks.
Sunless tanning delivers a faux glow by coating your skin with
the chemical dihydroxyacetone (DHA). DHA interacts with the dead
Sun Screen Review
* Choose a water-resistant, broad-
spectrum sunscreen with SPF 15
or higher.
* Apply an even coat of sunscreen
over all exposed skin, including
your eyelids, lips, nose, ears, neck,
hands and feet.
* Allow 15-30 minutes for the
sunscreen to be absorbed by your
skin before going outside.
* Reapply sunscreen according to
the directions on the label-usually
about once every hour.
FDA& YOU Page 6
surface cells in the epidermis to darken skin color and simulate a tan, and the result
usually last for several days. DID YOU KNOW?
You should know that while the FDA allows DHA to be "externally applied" for
skin coloring, there are restrictions on its use. DHA should not be inhaled, ingested,
or used in such a way that the eyes and eye area are exposed to it because the risks,
if any, are unknown.
Many self-tanners
don't have sunscreen
in them.
Check the label. If it
doesn't have sun-
screen, apply one with
SPF 15 or higher
before going outside
Before using a sunless tanning booth, ask the tanning salon these questions to
make sure you'll be protected:
Will my eyes and the area surrounding them be protected?
Will my nose, mouth and ears be protected?
Willi be protected from inhaling the tanning spray through my nose or mouth?
If the answer to any of these questions is "no," look for another salon. Otherwise you're putting yourself
at risk for exposure to chemicals with potentially dangerous effects.
You should also take precautions if you're applying a self-tanner at home. Most self tanners contain the
same DHA used in sunless tanning salons. Self-tanners are available in many forms, including lotions, creams
and sprays that you apply and let soak in to your skin. Follow the directions on the self-tanner label carefully
and take care not to get the self-tanner in your eyes, nose, or mouth.
Tanning Pills
You may have seen ads that promise to give you a golden glow just by swallowing a
pill. Tb.is may sound too good to be true, because it is. These, so-called, tanning pills are
unsafe and none are approved by the FDA
Some tanning pills contain the color additive canthaxanthin. When large amounts of canthaxanthin are
ingested, the substance can turn the skin a range of colors from orange to brown. They can also cause serious
health problems including liver damage; a severe itching
condition called urticaria; and an eye disorder called
canthaxanthin retinopathy, in which yellow deposits form
in the retinas.
Learn More
To learn more about UV rays, tanning, and sun safety
visit:
The Environmental Protection Agency's SunWise Web
site at http://www.epa.gov/sunwise.
The FDA's Web page on sunscreens, tanning products,
and sun safety at http://vm.cfsan.fda.gov/-dms/cos-220.html
VISIT OUR BOOTH
FDA & YOU will be exhibiting at the National
Association of Health Education Centers
(NAHEC) Conference in Houston, Texas
August 30 & 31 st
About FDA & You
FDA & You is an FDA publication to inform and encourage
health educators and students to learn about the latest FDA
medical device and health news.
The publication's contents may be freely reproduced.
Comments may be sent to the editors.
Editor: Alicia Witters
Editor: Edle Seligson
Email: FDAandyou@cdrh.fda.gov
Read us online at
hUp://www.fda.goy/cdrhlfdaandyou.html
Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health, HFZ-230
Rockville, MD 20850
Special thanks to
Sharon Miller, the OCER Radiation Experts and
Tammy Wallace
for contributing to this issue.
Issue Number 7- SPECIAL EDITION Summer2005
The Truth About Tanning:
What You Need to Know to Protect Your Skin
There's no such thing as a safe tan.
Don't mistake the tan you get from hours spent by the
pool or under tanning lamps for a healthy summer glow,
it's actually a sign of sun damage from UV rays and can
~ ~ cause premature aging and skin cancer. But protecting
your skin now can help prevent the side effects caused by
too much sun.
The Inescapable UV Ray
Ultraviolet (UV) radiation is all around us. The most common source is sunlight, which produces three main
types of UV rays: UVA, UVB, and UVC. While UVA and UVB rays are transmitted through the atmosphere, all
UVC and some UVB rays are absorbed by the Earth's ozone layer. Most of the UV rays that reach the Earth's surface
are composed of UVA with a small amount of UVB.
UV light is classified by wavelength. UVB rays have a sh01t wavelength that reaches the outer layer of your skin,
called the epidermis. UVA rays have a longer wavelength that can penetrate and damage the lower layer of your skin,
called the dermis. It's imp01tant to use protection when you're out in the sun
because both UVA and UVB rays can cause sunburn, premature aging, skin cancer,
and damage to the eyes and immune system.
Because UV rays are strongest fromlO a.m. until 4 p.m., it's a good idea to
check the Ultraviolet Index (UVI) before you go outside. UVI is a number from
1-11 that indicates the amount of skin-damaging UV rays reaching the eatth's sur-
face at any point in time. The daily UVI number, listed in the weather section of
most city newspapers, forecasts the amount of UV you'll be exposed to during the
sun's highest point in the sky-usually around noon. The higher the UVI number is,
the more intense the exposure. If your local newspaper doesn't list the UVI for your
area, the Envimnmental Protection Agency (EPA) offers UVI forecasts by ZIP code
at http://www.epa.gov/sunwise/uvindex. html.
When the UVI is 5 or higher, you should always protect yourself from UV
exposure with sunscreen, a brimmed hat, and sunglasses; taking extra care to
reapply sunscreen and seek shade or stay indoors. Also remember that exposure
doesn't come only from above; snow, sand, water, and even concrete reflect UV
In This Issue
The Inescapable UV Ray
Recipe for a Tan
Sunburn
Long-Term Sun Damage
Skin Cancer
Prevention
Sunscreen
In the Salon
Sunless Tanning
Tanning Pills
Learn More
FDA& YOU
rays. In addition, clouds don' t block UVB and you can still get sunburned on a
cloudy day. So it's important to wear sunscreen and protective gear in all types of
weather.
Recipe for a Tan
Page2
DID YOU KNOW?
Direct sun isn't the
only cause of sunburn.
Whether from a day on the beach or hours spent in a tanning salon, the "tan"
color your skin gets after baking under UV rays is a sign of skin damage.
You can get sun-
burned even on a
cloudy day because
UV rays can filter
through the water
droplets that make up
When it's exposed to UV rays your skin produces a pigment called melanin to
protect skin cells from damage. Melanin is the same pigment that already colors
your hair, eyes, and skin. When your skin is exposed to UV rays it produces extra
melanin and may become darker over the next few days.
clouds.
Contrary to what you may have heard, getting a tan doesn't protect your skin from further UV damage.
The extra melanin in tanned skin provides a Sun Protection Factor (SPF) of about 2 to 4; far below the
minimum recommended SPF of 15.
While it's true that sunlight can have the benefit of helping your body produce vitamin D, about 10 to 15
minutes of unprotected sun on your face and bands 2 to 3 times a week provides you with a healthy dose. Too
much sun exposure can lead to sunburn, premature aging, or skin cancer.
Sunburn
Like a tan, a sunburn is a sign of short-term sun damage. Sunburn, also called erythema, is the skin's
natural defense against overexposure to UV rays. When UV rays reach your skin they begin damaging skin
cells in the epidermis. In response, your immune system increases blood flow in the affected areas, making
the skin feel warm and look red. White blood cells, which help protect you from infection and disease, attack
and remove the damaged skin cells. The process of removing the damaged cells can cause the skin to itch and
peel. Meanwhile, the damaged skin cells are releasing chemicals that send messages to your brain. Your
brain translates these messages into a painful burning sensation to let you know you've been sunburned.
Because it can take up to 8 hours for the full effects of sunburn to kick in, you won't realize that you've
been burned right away.
A mild sunburn can be treated with cool baths, over-the-counter
hydrocortisone creams, and aspirin to ease pain and swelling,
according to the American Academy of Dermatology (AAD). A
severe sunburn, usually characterized by a large area of red,
blistered skin with a headache, fever, or chills should be treated
as a medical emergency and examined by a doctor right away.
Studies have shown a link between severe sunburn and
melanoma, the most serious form of skin cancer, so any
sunburn should been taken seriously.
Long-Term Sun Damage
Leathery, wrinkled skin and dark spots are
common earmarks of a lifelong sunbather.
Unfortunately, since these signs of sun damage
don't usually show up until many years later,
you may think you're immune to the long-term
effects of tanning.
FDA& YOU
Everyone, no matter their skin tone, is at risk
for skin damage. There are six skin categories
recognized by the FDA and the AAD. Each is
classified by sensitivity to the sun and typical
skin tone. Check out the table to see which skin
type you are.
The best way to prevent sun damage is to
practice sun safety everyday. That includes wear-
ing sunscreen, a brimmed bat, and sunglasses
every time you go outside. Remember, even if
you can't see it now, the damage done today will
catch up with you later.
Skin Cancer
According to the American Cancer Society,
"Many of the more than 1 million skin cancers
that are expected to be diagnosed in 2005 could
have been prevented by protection from the sun's
rays. "
Skin
Type
I
II
Ill
IV
v
VI
Page3
Sun History Example
Always burns easily, Red-headed, freckles,
never tans, extremely Irish/Scots/Welsh
sun sensitive skin
Always burns easily, Fair-skinned, fair-haired,
tans minimally, very sun blue or green-eyed,
sensitive skin Caucasians
Sometimes burns, tans Average skin
gradually to light brown,
sun sensitive skin
Burns minimally, always Mediterranean-type
tans to moderate brown, Caucasians
minimally sun sensitive
Rarely burns, tans well , Middle Eastern, some
sun insensitive skin Hispanics, some
African-Americans
Never burns, deeply pig- African-Americans
mented, sun insensitive
skin
Experts agree that natural and artificial sunlight, particularly the UV rays, damages the skin. UV rays
cause the obvious short-term damage seen in a sunburn or a tan, as well as the long-term damage that
accumulates with each exposure.
When you tan you greatly increase your risk of developing skin cancer. This is especially true if you
spend time tanning each year because damage to the skin accumulates over time. Unlike skin cancer,
premature aging of the skin will occur in everyone who is repeatedly exposed to the sun over a long time,
although the damage may be less apparent and take longer to show up in people with darker skin.
There are three main types of skin cancer: melanoma, basal cell carcinoma, and squamous cell carcinoma.
Melanoma is the least common but most serious because it's responsible for most of the skin cancer deaths
each year. The other two types, basal cell and squamous cell carcinomas, are often refened to as non-
melanoma skin cancer. Basal cell cancer is the most common skin cancer, followed by squamous cell carcino-
ma, which can also become a killer
A fourth type of growth, actinic or solar keratosis, is also of concern because it can progress into cancer.
It's the most common pre-malignant skin condition, occumng in more than 5 million Americans.
DID YOU KNOW?
Australia has the highest incidence
of skin cancer in the world. To make
it easy for Australians to remember
how to protect their skin,
The Cancer Council Victoria coined
the catchy slogan: Slip! Slop! Slap!
Slip! - Slip on a shirt
Slop! - Slop on SPF 15+ sunscreen
Slap! - Slap on a wide-brim hat
Researchers still aren't sure why some people develop skin cancer
and others don't, but there are some preventive measures you can
take that may reduce your chances of getting skin cancer. While sun-
screens protect against sunburn, they don't necessarily prevent cancer.
If you use sunscreens to spend more time in the sun, your skin could
still be exposed to a high dose of UV, especially the longwave rays.
So it's still a good idea to stay out of the sun at midday, and to protect
yourself with sunglasses, a wide-brim hat, and protective clothing like
a long-sleeved shirt made of thick, light-colored fabric.
Moles or freckles that change shape, color, texture, or get crusty
and bleed could be a sign of skin cancer. Early-stage melanomas
often show up as a light brown to black flat mark that is usually about
FDA& YOU Page 4
Perform A Self Skin Cancer Check
No matter how much time you spend in the sun, you should
protect yourself by checking for signs of skin cancer. Visit
http://www.fda.gov/cdrh/fdaandyou/issue03.html#7 to learn how.
one-quarter inch in size. Any suspect spot
should be checked out by your doctor as soon as
possible. When detected in its earliest stages,
skin cancer is often curable.
For more information on skin cancer, visit
the American Academy of Dermatology's Web
..._ ____________________ ___. site at http://www.aad.org.
Prevention
The best way to protect your skin from the dangerous effects of UV rays is to take simple precautions
every day. Wearing sunscreen, shielding your face and eyes with a wide-brim hat, and sunglasses with a
UV A/UVB rating of 99% or higher, and seeking shade when possible can help decrease your risk.
Clothing can also help protect you from harmful UV in the form of protection you don't need to reapply.
Fabrics can differ greatly in their ability to shield you from UV rays, and natural fibers like cotton offer little
protection when wet.
The ideal sun protective fabrics are lightweight, comfortable, and protect against exposure even when wet.
SPF clothing are available that have thick, tightly woven fabrics with special fibers and dyes to help shield
you from the sun's rays. Remember that light-color fabrics will be cooler in the summer heat.
Certain medications, such as antibiotics, can make you more sensitive to the sun and put you at greater
risk for sunburn. Ask your doctor whether you're taking a medication that could affect your sensitivity to the
sun and what you should do.
Sunscreen
Sunscreen doesn't completely protect you from harmful UV rays, but it can drastically reduce their effects
if used properly. Sunscreen is available in a variety of forms for you to choose from, including sprays, lotions,
gels and wax sticks. Most sunscreens are made of chemicals
that absorb UV radiation. Others create a banier that reflects
the UV radiation away from the skin.
When shopping for sunscreen, chose one that's labeled as
broad-spectrum because it will help protect you from both UVA
and UVB rays. Check the sunscreen label for broad-spectrum
ingredients, such as benzophenones (oxybenzone), cinnamates
(octylmethyl cinnamate and cinoxate), sulisobenzone, salicy-
lates, titanium dioxide, zinc oxide, and avobenzone (Parsol
1789).
All sunscreens are labeled with SPF numbers. The higher
the SPF number, the more protection against sunburn the sun-
screen provides. To get the most protection out of sunscreen
choose one with an SPF of at least 15.
Some sunscreens are labeled as being water-resistant.
These sunscreens stay on the skin longer even if they get wet
from pool water, ocean water, or sweat. But water-resistant
doesn't mean waterproof. Water-resistant sunscreens still need
to be reapplied, so check the label for reapplication times.
Protect Yourself with
These Sun Safety Tips:
* Avoid the sun, or seek shade, from 10 a.m.
to 4 p.m. when the sun's rays are
strongest.
* Apply an SPF 15 or higher sunscreen
* Al low 30 minutes for skin to absorb
sunscreen before going outside.
* Check the label and reapply sunscreen
according to the instructions.
* Wear a wide-brimmed hat.
* Protect eyes with sunglasses that have a
UV/UVB protection of at least 99%.
* Check with your doctor to find out if you're
taking medications that will make you
more sensitive to the sun.
FDA & YOU PageS
The effectiveness of a sunscreen is reduced if it's applied inconectly or if it's washed off, rubbed off, or
sweated off. To make sure you're getting the maximum sunscreen protection, apply an even layer of sunscreen
and reapply it according to the directions.
Sunscreen usually needs about 15-30 minutes to soak in to the skin before you go outside. Read the label
to see how long you should wait. If the label doesn't indicate how long, wait 30 minutes to be safe.
In the Salon
With the convenience offered by a tanning salon, it may be tempting to lie in a tanning bed or sit in front
of a tanning lamp. Fight the urge! Tanning beds and lights are just as dangerous as tanning at the pool or on
the beach. The UVA rays emitted by a tanning lamp or bed are often much more intense than those produced
by the sun. The aging and cancer risks associated with outdoor tanning are the same as tanning in a salon.
For these reasons, the FDA doesn't recommend the use of indoor tanning equipment--EVER
If you insist on using a tanning lamp or bed, follow these steps to reduce the dangers of UV exposure.
Be sure to wear the goggles provided, making sure they fit snugly and aren't cracked.
Start slowly and use short exposure times to build up a tan over time.
Follow manufacturer-recommended exposure times for your skin type. Check the label for exposure times.
Stick to your time limit.
After a tan is developed, tan no more often than twice a week.
The key is to take it slow. If you get the maximum exposure the
first time, you'll probably get burned. And because sunburn takes
several hours to develop you won't realize your skin is burned until
much later.
FDA has a radiation safety perfonnance standard for sunlamp
products. All sunlamp products must have a warning label, an
accurate timer, an emergency stop control, and include an exposure
schedule and protective goggles.
You should NOT use a tanning bed or lamp if:
You sunburn easily and don't tan. Skin that doesn't tan in the
sun probably won't tan with sunlamps either.
You get frequent cold sores. UV radiation may cause them to
appear more frequently.
You're taking medicines that can make you more sensitive to
UV rays. Check with your doctor or pharmacist.
Sunless Tanning
The spray-on glow offered at sunless tanning booths make them a
popular place to maintain a tan year-round. What you may not realize
is that even sunless tanning can have risks.
Sunless tanning delivers a faux glow by coating your skin with
the chemical dihydroxyacetone (DHA). DHA interacts with the dead
Sun Screen Review
* Choose a water-resistant, broad-
spectrum sunscreen with SPF 15
or higher.
* Apply an even coat of sunscreen
over all exposed skin, including
your eyelids, lips, nose, ears, neck,
hands and feet.
* Allow 15-30 minutes for the
sunscreen to be absorbed by your
skin before going outside.
* Reapply sunscreen according to
the directions on the label-usually
about once every hour.
FDA& YOU Page 6
surface cells in the epidermis to darken skin color and simulate a tan, and the result
usually last for several days. DID YOU KNOW?
You should know that while the FDA allows DHA to be "externally applied" for
skin coloring, there are restrictions on its use. DHA should not be inhaled, ingested,
or used in such a way that the eyes and eye area are exposed to it because the risks,
if any, are unknown.
Many self-tanners
don't have sunscreen
in them.
Check the label. If it
doesn't have sun-
screen, apply one with
SPF 15 or higher
before going outside
Before using a sunless tanning booth, ask the tanning salon these questions to
make sure you'll be protected:
Will my eyes and the area surrounding them be protected?
Will my nose, mouth and ears be protected?
Willi be protected from inhaling the tanning spray through my nose or mouth?
If the answer to any of these questions is "no," look for another salon. Otherwise you're putting yourself
at risk for exposure to chemicals with potentially dangerous effects.
You should also take precautions if you're applying a self-tanner at home. Most self tanners contain the
same DHA used in sunless tanning salons. Self-tanners are available in many forms, including lotions, creams
and sprays that you apply and let soak in to your skin. Follow the directions on the self-tanner label carefully
and take care not to get the self-tanner in your eyes, nose, or mouth.
Tanning Pills
You may have seen ads that promise to give you a golden glow just by swallowing a
pill. Tb.is may sound too good to be true, because it is. These, so-called, tanning pills are
unsafe and none are approved by the FDA
Some tanning pills contain the color additive canthaxanthin. When large amounts of canthaxanthin are
ingested, the substance can turn the skin a range of colors from orange to brown. They can also cause serious
health problems including liver damage; a severe itching
condition called urticaria; and an eye disorder called
canthaxanthin retinopathy, in which yellow deposits form
in the retinas.
Learn More
To learn more about UV rays, tanning, and sun safety
visit:
The Environmental Protection Agency's SunWise Web
site at http://www.epa.gov/sunwise.
The FDA's Web page on sunscreens, tanning products,
and sun safety at http://vm.cfsan.fda.gov/-dms/cos-220.html
VISIT OUR BOOTH
FDA & YOU will be exhibiting at the National
Association of Health Education Centers
(NAHEC) Conference in Houston, Texas
August 30 & 31 st
About FDA & You
FDA & You is an FDA publication to inform and encourage
health educators and students to learn about the latest FDA
medical device and health news.
The publication's contents may be freely reproduced.
Comments may be sent to the editors.
Editor: Alicia Witters
Editor: Edle Seligson
Email: FDAandyou@cdrh.fda.gov
Read us online at
hUp://www.fda.goy/cdrhlfdaandyou.html
Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health, HFZ-230
Rockville, MD 20850
Special thanks to
Sharon Miller, the OCER Radiation Experts and
Tammy Wallace
for contributing to this issue.
Department of Health and Human Services
Food and Drug Administration
5600 Fishers Lane (HFI-40)
Rockville, MD 20857
September 2000
(FDA) 99-1279
~ c = ~ ~ ~ ~ ~ ~ 0 ~ @
0 ~
~ ~ ~ ~ ~ ~ v ~ ~ ~
~ U.S. Food and Drug Administration
The Food and Drug
Administration, or FDA, is a
United States government agency.
FDA makes rules about many
products consumers use when
sunning or tanning.
These rules help protect the
health of consumers.
When Outside in
The Sun
Beware
Of the
Dangers
Harmful rays from the sun,
sunlamps and tanning beds may
cause:
skin cancer, which can be
deadly
eye problems
weakened ability to fight
disease
unsightly ski n spots
wtinkles and "leathery"
skin.
Take Extra Care
Be sure to follow the seven steps
to safer sunning especially if
you answer yes to any of
these questions:
( Do you have pale white skin?
-o Do you have blonde, red or light brown hair?
Were you ever treated for skin cancer?
() Has a family member ever had skin cancer?
-() Do you have an illness? If so, ask your doctor
about extra care.
()Do you take medicines? If so, ask your doctor
about extra care.
Give babies and children extra care in the sun.
Protect Yourself
With the Seven Steps
To Safer Sunning
1. Stay in the shade.
Avoid the sun from:
to
10 a.m. 4p.m.
This is when sun rays are strongest. Don' t be fooled
by cloudy skies. Harmful rays pass through clouds.
2. Use sunscreen
products on your skin.
Many suntan products have
sunscreens to protect your skin
from the sun.
Products with sunscreens have
an "SPF" number on the label.
SPF stands for Sun Protection
Factor. A higher number means
it protects longer. Buy products
with an SPF number of 15 or
more.
Buy products whose label also
says:
( "broad spectrum," meaning
it protects against the two
types of harmful sun rays
( "water resistant," meaning
it stays on your skin
longer, even if you get wet
or sweat a lot.
Follow These Tips
For Using Sunscreen Products
Put a sunscreen of at least SPF 15 on your skin
15 to 30 minutes before going outside.
Rub the sunscreen evenly on all uncovered skin.
Be sure to put it on your eyelids, lips, nose, ears,
neck, hands and feet. If you do not have much
hair, put it on the top of your head.
Do not get a sunscreen in your eyes. It can sting.
Once in a while, put on more sunscreen while
you're in the sun. Read the label to see how
often to put it on.
-( Do not use a sunscreen on babies under 6
months old.
On children older than 6 months, use a sunscreen
every time they go out.
3. Wear a hat.
A hat with a wide brim helps
shade the neck, ears, eyes, and
head.
4. Wear sunglasses.
Buy only sunglasses with a
label sayi ng the glasses block
99 to 100 percent of the sun's
rays. If there is no label, do not
buy the glasses.
5. Cover up.
Wear loose, lightweight, long-
sleeved shirts and long pants or
long skirts when in the sun.
6. A void artificial
tanning methods.
This includes sunlamps and
tanning beds, as well as tanning
pills and tanning makeup.
Tanning pills have a color
additive that turns your ski n
orange after you take them.
FDA has OK'd this color
additive for coloring foods but
not for ta1ming the skin. The
large amount of color additive
in tanning pills may be harmful.
Tanning makeup is put on the
skin to make it look tan.
Sometimes the color can be
washed off with soap and water.
Other times, it wears off after a
few days. These products are
not sunscreen lotions and will
not protect your skin from the
sun.
7. Check your skin
regularly for signs of
skin cancer.
Look for changes in the size,
shape, color or feel of
birthmarks, moles and spots.
If you find any changes or find
sores that are not healing, see
your doctor.
1. Look at the
back of your
neck and scalp
with the help of
a hand minor. 2. Look at your body-
front, back and sides-
in the minor.
3. Bend your
elbows and
look at the
undersides of
your arms.
5. Check parts that
are hard to see- like
your back- with
a hand minor.
4. Look at the
backs of your
legs and feet.
Do You Have More
Questions About
Safer Sunning?
Ask your doctor or other health-
care worker.
And ask FDA. There may be an
FDA office near you. Look for the
number in the blue pages of the
phone book.
You can also contact FDA
through its toll-free number,
1-888-INFOFDA
( 1-888-463-6332).
Or, on the World Wide Web at
www.fda.gov.
Cancer Epidemiology, l C ~
Biomarkers & Prevention
Tanning Beds, Sunlamps, and Risk of Cutaneous Malignant
Melanoma
Richard P. Gallagher, John J. Spinelli and Tim K. Lee
Cancer Epidemiol Biomarkers Prev 2005;14:562-566.
Updated version
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562 Cancer Epidemiology, Biomarkers & Prevent ion
Minireview
Tanning Beds, Sunlamps, and Risk of Cutaneous
Malignant Melanoma
Richard P. Gallagher,
1
'
2
,3 John J. Spinelli,
1
'
2
and Tim K. Lee l ,
4
' Cancer Control Research Program, British Columbia Cancer Agency; 'Department of Health Care and Epidemiology and
'Division of Dermatology, Faculty of Medicine, University of British Columbia, Vancouver, Canada;
and ' School of Computing Sciences, Simon Fraser University, Burnaby, Canada
Abstract
Background: A number of studies have been conducted
evaluating the risk of cutaneous malignant melanoma after
exposure to sunlamps and/or sunbeds. The proportion of
subjects in the individual studies who have reported
exposure has, in general, been modest, and the resulting
risk estimates for melanoma have been unstable with wide
95% confidence intervals (95% Cl). The inconclusive results
seen in individual studies have resulted in confusion as to
the carcinogenicity of these devices.
Methods: We conducted a systematic review and meta-
analysis of these studies. A review of the literature from Jan
1, 1984 to April 2004 using MEDLINE identified 12 case-
control studies and 1 cohort study which quantitatively
evaluated the use of sunlamps and/or sunbeds and subse-
quent melanoma. After applying exclusion/inclusion criteria,
9 case-control and 1 cohort study provided data for the
analysis. Summary odds ratios (OR) and 95% Cis for sunlamp/
Introduction
There is good experimental and epidemiologic evidence that
UV radiation exposure (mainly from sunlight) is causally
related to all forms of human skin cancer including cutaneous
ma)jgnant melanoma (1). Melanoma incidence has most
strongly and consistently been associated with reported
"intermittent sun exposure" mostly accrued through recrea-
tional activities. A quantitative review of studies of sun
exposure and melanoma found a positive association between
intermittent exposure and risk of cutaneous malignant
melanoma in 21 (statistically significant in 16) of 23 studies
included in the analysis (2}.
Because by its nature, exposure to artificial UV radiation
through sunlamp and sunbed use is intermittent in character,
there has been consistent concern over the past 15 years that
use of such devices for recreational tanning may increase risk
of melanoma (3). In addi tion, data from surveys conducted in
Europe (4, 5) and Nort h America (6) indicate that sunbeds are
now being used by an increasing proportion of the population,
particularly young people.
A series of epidemiologic investigations have attempted to
determine the nature of this putative association. However,
analysis of sunlamp/sunbed use has been hampered by small
Recei\ed 7 / 21J/ 04; revised 10/14/04; accepted 10/27/04.
Grant support: Michael Smith Fuundation for llealth Research ln1rastructure award.
The costs of publication of this artide were defrayed in part by the payment of page charges.
This article must therefore be hereby marked advertisement in accordance with 18 U.S.C.
Section 1734 solely to indicate this fact.
Requests for reprints: Richard P. Gallagher, Cancer Control Research Program, British
Columbia Cancer Agency, 600 West 10th Avenue, Vanc<>uver, BC, Canada VSZ 4E6.
Phone: 6048776000; Fax: 604-S77 1868. Email: richardgbccanccr.bc.ca
Copyright t'> 2005 American Association for Cancer Researd1.
sunbed use and subsequent melanoma were calculated using
a random-effect model.
Results: Ten studies provided data for assessment of melano-
ma risk among subjects who reported " ever" being exposed
compared with those " never'' exposed. A positive association
was found between exposure and risk (summary OR, 1.25;
95% Cl, 1.05-1.49). Significant heterogeneity between studies
was present. Evaluation of the metrics "first exposure as a
young adult" (5 studies) and ''longest duration or highest
frequency of exposure" (6 studies) also yielded significantly
elevated risk estimates (summary OR, 1.69; 95% Cl, 1.32-2.18,
and 1.61; 95% CJ, 1.21-2.12, respectively, with no heterogeneity
in either analysis).
Conclusions: Results indicate a significantly increased risk
of cutaneous melanoma subsequent to sunbed/sunlamp
exposure. (Cancer Epidemiol Biomarkers Prev 2005;14(3):
562- 6)
numbers of exposed subjects in individual studies. In order to
evaluate the strength and consistency of association between
use of these devices and melanoma, we have conducted a
systematic review and meta-analysis.
Materials and Methods
To identify relevant studies of sunbeds/sunlamps and
melanoma, we conducted a MEDLJNE database search for
the years 1984 to 2004, using the terms "melanoma (etiology,
epidemiology) and sunbeds, sw1lamps, and solarium" as
keywords. We also selected all review articles in English on
UV radiation, tanning devices, solaria, and melanoma, and
scrutinized these to locate articles with data on sunlamp and
sunbed use missed by the MEDLINE search. We did not
attempt to locate unpublished data. We chose 1984 as the
year of start of our search as that year saw the first
publications from large-scale epidemiologic studies of mela-
noma and UV exposure with good control for phenotype
confounders. The search yielded a total of 12 case-control
studies reporting risk estimates for melanoma subsequent to
sunbed/sunlamp use (7-18). In addition, one cohort study was
found which reported on usage among Norwegian and Swedish
women (19).
Selection of Studies. All case-control studies of cutaneous
malignant melanoma that reported on use of sunlamps,
sunbeds, or both were initially considered for the analysis.
For inclusion, we required that numbers (or percentages) of
exposed cases and controls were presented in the study, and
odds ratios (ORs) with 95% confidence intervals (95% Cl) were
Cancer Epidemiol Biomarkers Prev 2005;14(3). March 2005
Downloaded from cebp.aacrjournals.org on Apri l 9, 2013. 2005 American Association for Cancer Research.
available, evaluating at least "ever" versus "never" use of
these devices. Because of these requirements, two earlier
studies were omitted; one due to missing Cis (7) and the other
due to missing data on numbers of exposed cases and controls
(8). A study by MacKie et al. (10) was also omitted because it
was not possible from the information presented to determine
accurately the proportions or numbers of cases and controls
exposed. All other studies were included in the analysis.
In order to attempt to make the analysis reflect, as far as
possible, recreational rather than medical use of sunlamps/
sunbeds, we did not include studies of psoralen and UV A
radiation therapy [e.g., that of Stern et al. (20)]. Where studies
provided separate estimates of risk for medical and nonmed-
ical use, the estimates for nonmedical use were used. Where
separate estimates were not given, the overall ORs and Cis
were used. Whenever possible, ORs adjusted for phenotype
factors (hair, skin, eye color, phototype, number of nevi, etc.)
and sun exposure were used in preference to crude or
unadjusted values. The studies of Swerdlow et al (13) and
Osterlind et al. (9) present risk estimates as crude ORs
unadjusted for phenotype factors. Swerdlo"..,S indicated the
"ever versus never exposed" value was adjusted only for age,
sex, and region of residence. In the case of the study by Walter
et al. (14), risk estimates were calculated as crude and adjusted
ORs, and because the two analyses gave "essentially the same
effect" (p.236), the authors presented the unadjusted values.
Thus, the Walter estimates can be expected to closely
approximate adjusted values.
A number of the studies presented data which allowed us to
evaluate whether initial exposure to sunbeds/sunlamps
occurring earlier in life "as a young adult" conferred a
different risk than if exposure began closer to the time of the
study. A total of five studies contributed to this analysis and,
with the exception of the study of Walter et al. (14), the
estimates used were the adjusted values.
Finally, a number of studies attempted to determine
whether a dose-response gradient with exposure was seen.
We produced summary ORs comparing melanoma risk
between subjects with the longest duration or highest
frequency of exposure and subjects never exposed. Six studies
provided data for this analysis.
Two of the authors (R.P.G. and T.K.L.) examined each of the
studies independently to determine which risk estimate was
the best indicator of "first exposure as a young adult" and
which was the best for "longest duration or highest frequency
of use," and after a discussion concerning one study, agreed on
the measures considered to be most appropriate.
Summary ORs and 95% Cis were calculated for the three
measures of sunlamp/sunbed exposure noted above using the
method of DerSimonian and Laird (21). The Q statistic was
used as a test for heterogeneity among the original study
estimates (22). Published gender-specific ORs (14) or period-
specific ORs (15) were treated as separate entries or "studies"
in the meta-analysis. Sensitivity analyses were conducted by
recalculating summary ORs after eliminating specific studies.
Results
A total of 10 published articles (with 12 ORs) were used in
assessing the relationship betv.reen ever versus never use of
stmlamp/sunbed and melanoma (Table 1). The summary OR
showed a modest elevated risk (OR, 1.25i 95% Cl, 1.05-1.49).
Positive associations were seen in 8 of 10 individual studies,
although only 4 risk estimates were statistically significant.
One of the studies (9) showed an inverse association. There
5
Personal communication (April 30, 2004).
Cancer Epi demiology, Biomarkers & Prevention 563
was significant heterogeneity (Q = 28.9; P = 0.0024) likely due
to the studies being conducted over a long period of time with
different designs. Also, one study (9) showed results markedly
different from the others. Recalculation excluding the Oster-
lind study substantially reduced but did not eliminate the
heterogeneity, and had only a slight effect on the summary OR.
Excluding both the Osterlind study and the Swerdlow study
(not adjusted for phenotype factors) again had essentially no
effect (OR, 1.24; 95% CI, 1.09-1.41). The cohort study of Veierod
et al. (19) used "never/rarely" as the index in assessing
exposure. We included this measure in the analysis as
combining these two groups as the index should give a
conservative estimate of risk among users. Excluding the
Veierod study made little difference to the summary OR (OR,
1.21; 95% CI, 1.02-1.44).
Five studies contributed data to the analysis of first
exposure as a young adult (Table 2) which showed a positive
association with subsequent melanoma (OR, 1.69; 95% CI, 1.32-
2.18). Confidence intervals for this analysis were wider than
those seen for the previous metric because the estimates
contributing to the summary ORs were based on relatively
small numbers of subjects. All five of the individual studies
showed a positive association although only two were
statistically significant. This group of estimates showed no
evidence of heterogeneity (Q = 3.81; P = 0.58). Recalculation
excluding the Swerdlow study (no control for phenotype
factors) had only a slight effect on the summary measure (OR,
1.65; 95% CI, 1.28-2.13).
Data from six studies were entered into the analysis of
longest duration or highest frequency of use (Table 3). A
higher point estimate of risk was seen in this analysis (OR,
1.61; 95% CI, 1.21-2.12) than in the ever versus never analysis,
although the Cis for the two estimates overlapped slightly. All
six individual study estimates showed a positive association
with melanoma. Again, this group of estimates showed no
evidence of heterogeneity (Q = 5.90; P = 0.55), and recalcula-
tion excluding the Swerdlow study (no control for phenotype
factors) had virtually no effect on the summary OR (OR, 1.57i
95% CI, 1.19-2.09).
Discussion
This meta-analysis is subject to a number of limitations. The
estimates of risk for melanoma subsequent to using sunlamps/
sunbeds are based on published data in a series of 10 articles
over a period of 20 years. A pooled analysis of original
observations taken in the 10 studies would have provided a
more powerful approach to summarizing data on melanoma
and sunlamp/sunbed use. However, because the studies had
different overall aims, different metrics were used to record
duration and/or frequency of sunlamp/sunbed use. With the
exception of Westerdahl et al. (17), no study collected all the
information (years of use, frequency of exposure per year, and
duration of each exposure) needed to conduct a full quanti-
tative assessment of the association. This made pooling of raw
data infeasible.
Results of the analysis are, of course, dependent on the
choice of measures selected from each study. The overall
measure, ever versus never use, is fairly clear-cut, with the
caveat that we selected wherever possible the risk estimate
and Cis noted "for tanning purposes" rather than total use.
Recalculation of summary ORs using values for total sunbed/
sunlamp usage rather than use for tanning purposes
indicated that our decision did not affect the condusions
reached. The measures used to assess first exposure as a
young adult were subject to more judgment. The case-control
studies defined a young adult in different ways, with first
exposure ages ranging from "less than 25" to "less than 39
years." For the women's prospective cohort study (19), we
Cancer Epidemiol Biomarkers Prev 2005;14(3). March 2005
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564 Tanning Beds and Melanoma
Table 1. Exposure to sunlamps and/or sunbeds and cutaneous malignant melanoma: case control and cohort study results
Ever vs. never exposed
Reference Place and period Cases Controls % Controls exposed Metric
Osterlind East Denmark 1982-1985 474 926 18% Ever used sunbeds
et al. (9)
Swerdlow UK (Scotland) 1979-1984 180 197 8.3% Ever used UV lamps
et al. (13) or sunbeds
Walter Ontario Canada 1984-1986 583 608 Males 14% Ever used sunbeds/
et al. (14)
Females 21%
sunlamps
Garbe Germany 1984-1987 856 705 7% Use of stmbeds-yes
et al . (11)
Males 14%
Au tier Germany, Belgium, 420 447 Ever exposed
et al. (15) France 1991-1993 to sunlamps
Females 17"/}
for tanning
Ever exposed
to sunbeds
for tanning
Westerdahl South Sweden 1988-1990 400 640 25% Ever used sunbeds/
et al. (16)
38%11
sunlamps
Holly San Francisco USA 1981-1986 452 930 Ever use of sunlamp
et a.t. (12)
Chen Connecticut USA 1987-1989 624
et al. (18)
512 Males 16% Ever used sunlamp
Females 22"/c,
Westerdahl South Sweden 1995-1997 571 913 Males 33% Ever used stmbeds
et al. (17)
Females 57%
Veierod Sweden and Norway; Total cohort, 2% of total female Exposed 1 I mo
et al. (19) female cohort 1991-1999 106,379 women cohort exposed in anv month
at age 10-39
1
Summary OR
No. studies= 12 (10 investigations, 1 with sex-specific, and 1 with exposure-specific risk estimates)
NOTE: Abbreviation: NS, not stated.
*Odds ratio adjusted in the original study for age, sex, host factors, and in some studies, sun exposure.
tOdds ratio tmadjusted.
!Sunbed use only; no OR given for sunlamp use.
Used for tanning purposes.
II Study conducted among female subjects only.
tComparison group is never I rarely.
OR (95% CI)
0.7 t, t (0.5-1.0)
2.9 t (1.3-6.4)
Males 1.88 t (1.20-2.98)
Females 1.45t (0.99-2.13)
M + F 1.62t (1.21-2.16)
1.5* (0.9-2.4)
1.77t (1.00-3.23)
Sunbeds 0.95t (0.64-1.41)
Ails 1.16 t (0.83-1.61)
1.3* (0.9-1.8)
0.94 t (0.74-1.2)
1.13* (0.82-1.54)
1.2 (0.9-1.6)
1.55* (1.04-2.32)
1.25 (1.05-1.49)
defined first exposure as a young adult to be women who
used sunbeds for the first time at ages 10 to 19. As this cohort
was comprised of women who were recruited in 1991 to 1992
at ages 30 to 50, early exposure would have occurred
before 1980.
The longest duration or highest frequency of use analysis
combined what we considered to be the best measure of
cumulative sunbed/sunlamp exposure available within each
study. The intention of this analysis was to compare risk
estimates in subjects with maximal cumulative usage to that in
Table 2. Exposure to sunlamps and/or sunbeds and cutaneous malignant melanoma: case control and cohort studies
First exposure as young adult
Reference Place and period Cases Controls % Controls exposed
Swerdlow UK (Scotland) 1979-1984 180 197 3%
et a!. (13)
Walter Ontario Canada 1984-1986 583 608 Males 7%
et a!. (14)
Females 12%
Chen Connecticut USA 1987-1989 624 512 8%
et al. (18)
Westerdahl South Sweden 1995-1997 571 913 9%
et al. (17)
2% of total female
cohort
Veierod Sweden and Norway; Total cohort
et a!. (19) female cohort 1991-1999 106,379 women
Summary OR
No. studies = 6 (5 studies, 1 with sex-separate risk estimates)
*Odds ratio adjusted in the original studies for age, sex, host factors, and in some studies, stm exposure.
t Odds ratio tmadjusted.
Metric
Age at first
exposure <30 y
First use
<age 30
<age 25 at first use
of sunlamp
First exposure at
age !!35
Exposed
age 10-19
Cancer Epidemiol Biomarkers Prev 2005;14(3). March 2005
OR* (95% CI)
3.8 (0.9-16.5)
Males 2.13
1
(1.13-4.13)
Females 1.55 t (0.94-2.59)
M +,F 1.75t (1.18-2.59)
1.35 (0.88-2.08)
2.3* (1.2-4.2)
1.52* (0.56-4.12)
1.69 (1.32-2.18)
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Cancer Epidemiology, Biomarkers & Prevention 565
Table 3. Exposure to sunlamps and/or sunbeds and cutaneous malignant melanoma: case control and cohort studies
Longest duration or highest frequency of use
Reference Place and Period Cases Controls % Controls Exposed Metric OR 95% CI)
Swerdlow et al. (13) UK (Scotland) 1979-1984 180 197 2% Duration of use > 1 y 3.4* (0.6-20.3)
Walter et al. (14) Ontari o, Canada 1984-1986 583 608 Males 4% Sunbed/sunlamp use Males 2.12
1
(0.90-5.28)
:;::1/mo for :;::12 mo
Females 2% Females 2.99
1
(1.08-9.57)
M + F 2.44
1
(1.27-4.71)
Au tier et al. (15) Gennany, Belgium, 420 447 Prior to 1980 5% ;;:: 10 h exposure for Prior to 1980 2.12 (0.84-5.37)
France 1991-1993 tanning before 1980
1980 or later 2% :;::10 h exposure for 1980 or later 0.99* (0.49-2.00)
South Sweden 1988-1990
tanning 1980 or later
1.8* (1.0-3.2) Westerdahl et al. (16) 400 640 5% >10 exposures/y to
sunbeds/sunlamps
1.1f (0.60-2.20) Chen et al. (18) Connecticut USA 1987-1989 624 512 8% 2:10 uses of sunlamp
Westerdahl et al. (17) South Sweden 1995-1997 571 913 6% >250 sunbed uses 1.5 (0.7-3.2)
Summary OR
No. studies = 8 (6 studies, 1 with sex-specific estimates, and one with period-specific estimates) 1.61 (1.21-2.12)
*Odds ratio adjusted in the original studies for age, sex, host factors, and in some studies, sun exposure.
tOdds ratio unadjusted.
subjects "ever exposed" and those "never exposed." This
would enable us to determine whether there was a suggestion
of a gradient of risk from none to maximal use. Of course those
subjects most heavily exposed will also be included in the ever
exposed category, so the OR differences seen between the
levels of exposure are not independent.
The published articles covered a time period of nearly 20
years. During this time the UV emissions of artificial tanning
devices changed in character. Stmlamps used up to the late
1970s were usually used in the home setting (except for
medical use) and emitted primarily UVB (sometimes with a
small component of UVC). Tn the early 1980s, two major
changes took place. Indoor tanning began to be done largely in
commercial salons rather than at home, and salons began to
use VV A lamps. Thus, the character of the exposure changed
and because of this there is some question whether results
from the early studies (9, 13, 14) can be legitimately combined
with those of more recent studies. We suggest that combining
the results of the studies is appropriate, as there is no
convincing human data demonstrating that UVB is more or
less strongly related to melanoma than UV A. Tn fact, there is
some evidence that melanocytes exposed in vivo to either UV A
or to UVB show similar levels of thymine dimer formation (23).
In addition, studies have shown that UV A as well as UVB
impairs antioxidant function and promotes reactive oxygen
species, events known to be involved in cutaneous carcino-
genesis (24-27). Finally, the risk estimates from later studies,
taken together, do not differ in character from those seen in the
earlier investigations.
Finally, although we have used risk estimates adjusted for
phenotype factors and, when possible, for sun exposure, it is
unlikely that the studies have achieved complete control for
these potential confounders. If individuals who use artificial
tanning devices are more likely to suntan, as many suspect,
then some of the elevated risk seen might be due to
recreational sun tanning.
Our results, however, suggest that any exposure to artificial
tanning devices modestly, but significantly, increases risk of
cutaneous melanoma; however, caution is needed as it is
possible that there is unpublished (or unanalyzed) data on
sunbed or sunlamp use in existence from previously con-
ducted etiologic studies of melanoma. The subgroup analysis
of risk among those exposed "early in adult life" suggests a
risk estimate slightly higher than that seen in the ever versus
never analysis. We take this to indicate that risk increases with
adequate lag time (>10 years) after commencement of
exposure. However, as noted above, this lag time is potentially
confounded by the change in tanning device emissions from
UVB to UVA in the early 1980s. The latter interpretation,
however, seems unlikely as tisk estimates for exposure during
the period when UVA was emitted by sunbeds (17) are similar
to those seen during earlier periods.
Summary ORs for those with the longest duration or highest
frequency of use suggest a higher risk of melanoma among
those most heavily exposed than among those ever exposed.
Confidence intervals of the two estimates overlap; however,
this does give some indication that a dose-response effect
might be found to be present if exposure data were more
effectively captured.
Tf there is a causal relationship between stmlamp I sunbed
exposure and melanoma, the public health question is asked:
how important is the risk? It is not possible with the data
available to answer this question wi th any certainty. However,
a large number of epidemiologic studies have been conducted
on the relationship betvveen solar UV exposure and melanoma,
and these have been summarized quantitatively by Nelemans
et al. (28) and Elwood and Jopson (2). Combining the highest
reported levels of "intermittent" exposure produced a sum-
mary OR for all studies of 1.71 (95% CI, 1.54-1.90) in the
Elwood study, and 1.57 (95% CI, 1.29-1.91) for population-
based studies in the Nelemans investigation. These values are
similar to that seen for longest duration or highest frequency of
use of sunlamps/sunbeds in the present study. Although
caution is required due to the possibility of confounding by
inadequate control for concurrent sun exposure, the results
suggest that artificial UV may be a significant contributor to
risk among those with substantial exposure.
In summary, although it is not possible to determine
accurately how much sunbed/sunlamp use contributes to
individual risk of cutaneous malignant melanoma, it seems
clear that any use of these devices elevates risk for cutaneous
malignant melanoma. Furthermore, risk further increases
with appropriate lag tin1e, and frequency and duration of
use seem likely to be positi vely related to the magnitude of
the risk.
References
1. International Agency for Research on Cancer. !ARC monographs on the
evaluation of carcinogenic risk to humans. Vol 55. Solar and ultraviolet
radiation. Lyon: !ARC Press; 1992.
2. Elwood JM, jopson j. Melanoma and sun exposure; an overview of
pubUshed studies. Int J Cancer 1997;73:198-203.
3. Young AR. Tanning devices-fast track to skin cancer? Pigment Cell Res
2004;17:2- 9.
Cancer Epidemiol Biomarkers Prev 2005;14(3). March 2005
Downloaded from cebp.aacrjournals.org on April 9, 2013. 2005 American Association for Cancer Research.
566 Tanning Beds and Melanoma
4. Amir Z, Wright A, Kernohan E, Har t G. Attitudes, beliefs and behavior
regarding the use of sunbeds among healthcare workers in Bradford. Eur
} Cancer Care 2000;9:76- 9.
5. }erkegren E, Sandreiser L, Brandberg Y, Rosdahl I. Sun-related behavior and
melanoma awareness among Swedish university students. Eur } Cancer
Prev 1999;8:27 -34.
6. Geller AC, Colditz G, Oliveria S, et al. Use of sunscreen, sunburning rates,
and tanning bed use among more than 10000 US children and adolescents.
Pediatrics 2002;109:1009 - 14.
7. Gallagher RP, Elwood }M, Hill GB. Risk factors for cutaneous malignant
melanoma: the western Canada melanoma study. Recent Results Cancer Res
1986;102:38-55.
8. Holman CDJ, Armstrong BK, Heenan P}, et al. The causes of malignant
melanoma: r ~ s u l t s from the West Australian Lions melanoma rt-search
project. Recent Results Cancer Res 1986;102:18- 37.
9. Osterlind A, Tucker MA, Stone B}, Jensen OM. The Danish case-control
study of cutaneous malignant melanoma: II. Importance of UV light
exposure. lnt J Cancer 1988;42:319 - 24.
10. MacKie RM, Frcudenberger T, Aitchison TC. Personal risk-factor chart for
cutaneous melanoma. Lancet 1989;2:487 - 90.
11. Garbe C, Weiss J, Kruger S, et al. The German Melanoma Registry and
environmental risk factors implied. Recent Results Cancer Res 1993;128:
69- 89.
U . Holly EA, Aston DA, Cress R, Ahn OK, Kristiansen JJ. Cutaneous melanoma
in women I. Exposure to sunlight, abili ty to tan, and other risk factors
related to ultraviolet light. Am J Epidemiol1995;141:923-33.
13. Swerdlow A}, English }S, MacKie RM, et al. Fluorescent lights, ultraviolet
lamps, and risk of cutaneous melanoma. BM} 1988;297:647-50.
14. Walter SO, Marrett LD, From L, Ht,rtzman C, Sharmon HS, Roy P. The
association of cutaneous malignant melanoma with use of sunbeds and
sunlamps. Am J Epidemiol 1990;131:232-43.
15. Autier P, Dore JF, Lejeune F, et al. Cutaneous malignant melanoma and
exposure to sunlamps and sunbeds: an EORTC multicentre case-control
study in Belgium, France and Germany. lnt J Cancer 1994;58:809- 13.
16. Westerdahl }, Olsson H, Masback A, et al. Use of sunbeds or sunlamps and
malignant melanoma in Southern Sweden. Am J Epidemiol 1994;140:691-9.
17. Westerdahl }, lngvar C, Masback A, Jonsson N, Olsson H. Risk of
cutaneous malignant melanoma in relation to use of sunbeds: further
evidence for UV-A carcinogenicity. Br } Cancer 2000;82:1593- 9.
18. Chen YT, Dubrow R, Zheng T, Barnhill RL, Fine J, Berwick M. Sunlamp use
and risk of cutaneous malignant melanoma: a population-based, case-
control study in Connecticut USA. lnt} Epidemiol 1998;27:758-65.
19. Veierod M13, Weiderpass E, Thorn M, et al. A prospective study of
pigmentation, sun exposure, and risk of cutaneous malignant melanoma in
women. J Nat! Cancer Inst 2003;95:1530-8.
20. Stern RS, Nichols KT, Vakeva LH; for the PUVA Follow-up Study.
Malignant melanoma in patients treated for psoriasis with methoxsalen
(psoralen} a.nd ultraviolet A radiation (PUVA}. N Eng! J Med 1997;336:
1041- 5.
21. DerSin1onian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials
1986;7:177 - 88.
22. Petitti DB. Meta-analysis, decision analysis, and cost effectiveness analysis:
methods for quantitative medicine. New York: Oxford University Press;
1994.
23. Young AR, Potten CS, Nikaido 0, et al. Human melanocytes and
keratinocytes exposed to UVB or UVA in viw show comparable levels of
thymine dimers. J Invest Dermatol 1998;111:936-40.
24. Fuchs J, Huflejt, Rothfuss LM, Wilson OS, Carcamo G, Packer L. Acute
effects of near ultraviolet and visible light on the cutaneous antioxidant
system. Photochem Photobiol1989;50:739- 44.
25. Fuchs }, Huflejt ME, Rothfuss LM, Wilson OS, Carcamo G, Packer L.
Impairment of enzymatic and nonenzymatic antioxidants in skin by UVB
irradiation. J Invest Dermatol1989;93:769-73.
26. Sander CS, Hamm F, Elsner P, Thiele JJ. Oxidative stress in mal ignant
melanoma and non-melanoma skin cancer. Br J Dermatol 2003;148:
913- 22.
27. Sander CS, Chang H, Hamm F, Elsner P, Thiele JJ . Role of oxidative stress
and the antioxidant network in cutaneous carcinogenesis. Int J Dermatol
2004;43:326- 35.
28. Nelemans PJ, Rampen FHJ, Ruiter OJ, Verbeek ALM. An addition to the
controversy on sunlight exposure and melanoma risk. J Clin Epidemiol
1995;48:1331-42.
Cancer Epidemiol Biomarkers Prev 2005;14(3). March 2005
Downloaded from cebp.aacrjournals.org on Apri l 9, 2013. 2005 American Association for Cancer Research.
A Preliminary Investigation of the
Predictors of Tanning Dependence
Carolyn J. Heckman, PhD; Brian L. Egleston, PhD; Diane B. \Vilson, EdD, RD;
Karen S. lngersoll, PhD
Objectives: To investigate pos-
sible predictors of tanning depen-
dence including demographic vari-
ables, exposure and protective be-
haviors, and other health-related
behaviors. Methods: This study con-
sisted of an online survey of 400
students and other volunteers from
a university community. Results:
Twenty-seven percent of the
sample was classified as tanning
dependent. Tanning dependence
S
kin cancer is the most common
form of cancer in the United States,
accounting for half of all human
cancers, ' with over a million new cases
diagnosed yearly. Nmety percent of all
skin cancers are due to ultraviolet radia-
tion (UVR) .
2
Thanks to recent media at-
tention. the US public has demonstrated
increased awareness of the harmful ef-
fects of UVR.' Unfortunately, studies have
also demonstrated that people. particu-
larly young adults. continue to use mmi-
Carolyn J Heckman, Assoetate Member. Popu
latron Scrence, Fox Chase Cancer Center,
Cheltenham, PA. Brian L. Egleston, As:srstant
Member, Brostatisttcs Faetlity, Fox Cha!;e Cancer
Center, Pluladelpltra, PA. Drane B. Wrlson, Asso
crate Professor, Department of Internal Medrcrne,
Virgmra Commonwealth Umuersity Richmond. VA
Karen S. Ingersoll. Assocrate Professor, Depart
ment of Psychratnc Medretne, University of Vrr
grnra Center for Addrctron Research and Educa
tron, Charlottesvrlle, VA.
Address correspondence to Dr Heckman, Popu-
lattOII Snence, Fox Chase Cancer Center, 510
Tow11shrplrne Rd. First Floor, Cheltenham, PA
19012. Email: Carolyn.lleckmanrafccc edu
Am J Health Bebn ."" 2 008;32(5):451-464
was predicted by ethnicity and skin
type, indoor and outdoor tanning
and burning, and lower skin protec
tive behavi ors, as well as smoking
and body mass index. Conclusions:
Young adults are at risk for tanning
dependence, which can be pre-
dicted by specific demographic and
behavioral variables.
Key words: tanning, skin can-
cer prevention, addiction
Am J Healt h &hav. 2008;32(5):451-464
mal skin protection strategies yet re-
ceive large amounts of intentional and
incidental exposure to UVR, either
through sun exposure or from the use of
tanmng salons
1 7
As suggested by the
continued exposure to UVR \vithout ad-
equate protection despttt increasmg
awareness of risks, clearly there are
strong motivations for such exposure and/
or Significant barriers to engaging in pro
tecbve behaviors. Most of the recent lit-
erature suggests that the effect on ap-
pearance ts the pnmary motivation for
sunbathing and tanning booth use . .l-
11
It is
no wonder then that educational mter-
ventions targeting skin safety and can-
cer knowledge have fallen short in terms
of changing actual tanning behavior.
11 1
"
However, there may be some indtviduals
who tan excessively for reasons other
than appearance Like other health risk
behaviors. tannmg behtwtor probably has
multiple determinants.
Similarities between excessive tan-
ning dnd substance use disorders or ad-
diction have been discussed formally in
the literature recently and anecdotally
for years.
17
In the lay media, the term
451
Tanning Dependence
tanorexia has been used to describe a
preoccupation with the desire to be tan
paired wi.th excessive tanning, similar to
anorexia nervosa or an obsessive desire
to be thin paired wi.th compulsive dietary
behavior.
18
Tanorexia is illustrated by the
recent explosion in media images of tan
celebnties
18
and numbers of tanning sa-
lons'1Q as well as sunless tanning prod-
ucts on the market. However, tanorexia
may be a misnomer, as substance depen-
dence or addiction may be a better model
for understanding excessive tanmng than
an eating disorder model.
Several similarities exist between tan-
ning and substance use. They are both
prevalent in youth, are often initially
perceived as image enhancing, and are
health-risk behaviors that people partici-
pate in despite warnings.
20 25
A primary
motivation for tanning behavior is ap-
pearance enhancement. However, tan
ners report other benefits such as mood
enhancement, relaxation, and socializa
hon, also consistent with addiction in
which behaviors are reinforcing in spe-
cific, pleasurable ways.
26
-
28
For example,
Hillhouse and TurrisP
1
have found that a
subset of uhardcore" frequent tanners
have seasonal affective disorder. These
individuals may be using tanning for self-
medication purposes.
A possible mechanism for tanning de-
pendence (TD) is the release of endog-
enous opioids during UVR exposure.2b.n
2910
There is some evidence supporting this
hypothesis.
21
'
21

111 30
Feldman et aP
6
investi-
gated UVR as a reinforcer among 14 regu-
lar indoor tanners. The participants dem-
onstrated a preference for a UVR versus a
non-UVR tanning bed despite successful
blinding in terms of visual or tactile cues.
UVR exposure was associated with a more
relaxed and less tense mood than non-
UVR exposure. Kaur et al'
7
compared 8
frequent and 8 infrequent tanners. Fre-
quent tanners demonstrated a prefer-
ence for a UVR versus a non-UVR tanning
bed. This preference was reduced with
increasing doses of naltrexone, an opioid
antagonist. Moreover, as the dose in-
creased, 4 of the 8 frequent tanners expe-
nenced withdrawal-like symptoms (nau-
sea and/or jitteriness), and 2 dropped out
of the study entirely due to these symp-
toms. Infrequent tanners demonstrated
less preference for the UVR bed and re-
ported no adverse events at any dose of
naltrexone. These withdrawal symptoms,
452
dose-response relationship, and opioid an-
tagonism are reminiscent of traditional
substance use disorders. However, al-
though 2 studies found increased plasma
levels of endorphins during UVR expo-
sure,
2
!1
30
2 other studies have failed to
demonstrate this effect. J J < t
A few other studies have noted associa-
tions and similarities between tanning
and substance use. Demko et al
22
found
that among 6903 nationally representa-
tive white adolescents, those who used 2
or 3 substances were 3 times more likely
to be indoor tanners than others. Several
other studies have found relationships
between tanning and substance use such
as cigarette smoking.
24 13
Zeller et aP
5
found that 29% of a sample of 267 teens
aged 14- 17 who tanned indoors more than
once in the last year reported that they
would have difficulty quitting indoor tan-
ning. Variables associated with antici-
pated quitting difficulty were younger age
at initiation and higher frequency of use,
characteristics often found among sub-
stance-dependent individuals
In another attempt to explore a possible
relationship between excessive tanning
and addiction, Warthan et al
17
modified
the substance dependence criteria from
the American Psychiatric Association's
Diagnostic and Statistical Manual-1V-
TR34 (DSM-IV-TR) and those of the 4-item
CAGE scale,
35
traditionally used to screen
for potential problems with alcohol use.
CAGE is an acronym that refers to the 4
yes or no items regarding trying to Cut
down on drinking (or in this case tan-
ning), feeling Annoyed when told not to do
a behavior, feeling Guilty when doing the
behavior too much, and wanting to par-
ticipate in the behavior first thing in the
morning (Eye opener). Using these scales,
Warthan et a1
17
found that in a sample of
145 Texas beachgoers, 26% met the modi-
fied CAGE criteria and 53% met the modi-
fied DSM-IV-TR criteria for tanning de-
pendence. Using a chi -square test,
Warthan et al
17
found that the results
from the 2 scales "were significantly as-
sociated (P = .03, p 964)." Their study
provides some evidence for construct va-
lidity in that women were more likely to
have positive CAGE resuJts, and partici-
pants who scored positive on the DSM-lV-
TR reported tanning more often and going
to the beach more often to tan than did
others. Likewise, Poorsattar and
Hornung
28
found that 12% of their under-
graduate sample met the CAGE criteria.
Based on our review of the literature.
no other psychometric studies have been
conducted on these TO measures, but
prc\ious studies have examined the psy-
chometrics of the CAGE and DSM-IV-TR
criteria for substance disorder screening
and diagnosis. A number of studies have
demonstrated good reliability, sensitivity
(77-86%). specificity (93 94%), and valid-
ity of the CAGE to screen for alcohol disor-
ders. 3631 There are several strong nnd
widely used instruments used to Q!;Sess
DSM-IV criteria for the diagnosis of sub-
stance dependence. For example, the
Structured Clinical Interview for DSM-IV
(SCIO) and the Composite InternatiOnal
Diagnostic i nterview (CIDJ) have been
found to have excellent interrater reh
ability, good test-retest reliability, and
superior validity to standard clinical in-
There 1s much more cvt-
dence supporting the use of DSM-IV crite-
ria for dtagnosis of sub:itance dependence
than for use of the CAGE screener How-
ever, DSM TV measures are typicnUy no
ministered as structured interviews
rather than questionnaires as was done
with the TO measure in the study by
Warthan ct al.
17
The purpose of the current study was to
replicate and extend the work of Warthan
et nP
7
by further investigating possible
predictors of tanning dependence such as
demographic variables, exposure and pro-
tective behaviors, and other health -re-
lated behaviors (smoktng and exercise)
in a general young adult sample. We wen
interested in demographic associations
with tanning dependence that might be
used clinically to identify individuals at
risk of being or becoming tanning depen-
dent. We were also interested m sun
exposure and protective associations with
tanning dependence that might support
the construct validity of the tannmg de-
pendence measures. Finally, we were
mterested in the other health behaviors
potentially related to tanning dependence
that might provide insight into the type of
theoretical model most applicable to indi -
viduals who are preoccupied with tan-
ning.
METHODS
Participants
Participants were students and other
volunteers (n = 400) from a
metropolitan university community who
Am J Health Behav."" 2008;32(5):451-464
Heckman et al
were recruited during the 2006 spnng
semester. College-aged panlc!pants were
selected for this studv because teens and
young adults are known to be frequent
tanners and at risk for substance abuse
and dependence.
821

40
...
3
Participants were
recruited from the community in addi-
tion to the Psychology 10 l subject pool in
order to enhance gcncrahzability.
Meaaurea
Tanning dependence. Wnrthnn et o.l '
7
modified CAGE and DSM-!V-TR
(mCAGE and mDSM-IV-TR) were used to
measure TO. These mstruments are the
only formal scales currently available to
measure the construct. As ment1oned
previously, CAGE is an acronym that re-
fers to the 4 yes or no items regarding
unsuccessful attempts at Cutting down,
Annoyance with admonitions, Guilt about
the behavior, and using the behavior as
an Eye-opener. The modified 7-item DSM-
IV-TR critena address tolerance, with-
drawn!, and tanning despite negative con-
sequences, key criteria of substance de-
pendence. Sample items nrc "Do you think
you need to spend more and more time m
the sun to maintain your perfect tan?",
woo you continue tannmg so your tan Will
not fade?", "Does this !your belief that
tannmg cnn cause skin cancer! keep you
from :.pending time m the sun or going to
tanning beds?" Most of the mDSM-IV TR
items had yes or no responses, but 2
items asked about days per week spent
tanning m salons and the sun. Scoring
was conducted as in the study by Wanhan
et al
17
in which 2 or more positive items
on the mCAGE or 3 or more on the mDSM-
IV-TR were deemed to indicate TD. This
sconng scheme is the same that is used
for substance dependence screening with
the original measure,
Demographic variables. Panicipants
repor <'d their sex, age, year in school ,
racef ethntcity, whether they were psy-
chology students, and thctr likelihood of
burning nnd tnnning. Their skin type wns
classified according to

There
arc 6 skin types with 1'ype I being the
fairest t:lnd most likely to burn and Type VI
bemg t ne darkest and lenst likely to burn
Outdoor tanning, indoor tanning,
and s kin protection. The following item!->
scales were modified from simtlar ones in
the liternture.
154
f>.S
1
Participants were que-
ried about their level of intentional and
incid1ntnl summer sun exposure, tan-
453
Tanning Dependence
ning booth use, and chemical sunless
tanner use. A protective behaviors scale
was used to assess a range of skin protec-
tion behaviors: wearing clothing, staying
in the shade, avoiding or limiting midday
sun, and using sunscreen. The scale had
7 Likert-type items ranging from 1 a
never to 5 always use such protection,
for a possible range of scores from 7 to 35.
This scale was divided into tertiles (low,
medium, and high protection) for the lo-
gistc regression analyses.
Other health-related behaviors. ln or-
der to perform a preliminary assessment
of other potential health-related predictors
of TO, ever or current use of tobacco and
exerctsc ttems from the Center for Dis-
ease Control and Prevention's 1995 Na-
tional College Health Risk Behavior Sur-
vey were The following items were
divided mto tertiles (low, medium, high):
body mass index (via self-report height and
weight), days per week exercismg aerobi-
cally, and days per week exercising anaero-
bically (strengthening or toning muscles).
Procedures
The current study was an online survey
of volunteer participants from a university
community. Participants were recruited
Vta a university psychology student subject
pool, flyers. and advertisements Students
went to a website to choose the
experiments, and if they selected the cur-
rent study, they were connected directly to
the survey URL. The URL was also posted
on flyers and ads around the university and
surrounding area so that other commu-
nity members could access it. Psychology
1 01 students could earn research pomts
for their classes by signing up for any of a
variety of experiments. A raffle for depart-
ment store merchandise gift cards was
offered as an incenuve. This study was
approved by the university institutional
review board.
Analyaea
The purpose of the analyses was to
identify predictors of TO as measured by
Warthan et al's
17
modified substance de-
pendence scales. Three separate mul-
tiple logistic regression models were cre-
ated to predict TO: one including demo-
graphic variables, one including other
UVR exposure and protective behaviors,
and one including other health behavior
variables. We used 3 regressions to sepa-
rately investigate ( 1) the demographic
454
variables associated with tanning depen-
dence, (2) the UVR-related behavior vari-
ables that would support the construct
validity of tanning dependence, and (3)
the other health- related variables that
would indicate the type of theoretical model
(for example, eating disorder versus ad-
diction) that would be most associated
with tanning preoccupation. For ease of
presentation and to allow for nonlinear
effects, we categorized continuous van-
abies into 3-level ordinal variables repre-
senting low, moderate, and high values of
the variables. For the 2 continuous UVR-
related variables that were found to be
stati&tically associated with tanning de-
pendence when categorized, we refit the
models but included the 2 variables using
restricted cubic spliness.. with knots (cut-
points allowing changes in the underly-
ing basis curves) at the same cut-points
as used to create the categorical vari-
ables. We used figures to display the ef-
fects of the variables on tanning depen-
dence when entered into the model using
restricted cubic splines. Restricted cubic
splines are a more flexible method of
modeling nonlinear effects than the m-
clusion of categonzed continuous vari-
ables in regressions. Although restricted
cubic splines allow for better estimation
of nonlinear effects, the parameters from
the models in which they are included
are largely uninterpretable due to the
scaling of the spline basis functions. For
this reason, we present the point esti-
mates of the parameters when the vari-
ables were categorized, but display the
impact from the spline models visually to
give a more accurate representation of
the relationship of the variables with
tanmng dependence.
Our study had power to detect modest
effects; with the distribution of tanning
dependent and nondependent participants
in our study, we had 80% power to detect
an apprmamate 0.3 unit standardized ef-
fect (a standardized effect is an effect in
standard deviation units) between the 2
groups using a t-test with a 2-sided hy-
pothesis test and a 5% Type I error rate
and 90% power to detect an approximate
0.4 unit standardized effect. Cohen!>4 has
defined a small effect as one of 0.2 stan-
dardized units and a medtum one of 0.5
units. We did not power the study explic-
itly to detect effects m a multiple logistic
regression. Hence, the findings from the
regression analyses should be consid-
Heckman et a1
Table 1
Participant Characteristics by Tanning Dependence (N=400)
Dependent
(n)
O"erall Sample 26.5 ( 106)
t"cmale St>x 77 (82}
Psycbolol!) 101 711 (H3)
ht \ ear St udent 60 (64)
\\hlte
85 (90)
Finpotrlck Skin f ) Jlt.'
1 7 (7)
2 10 (II)
'
26 (28)
4 29 (31}
5 26 (28)
6
I (I l
Sunles l.ast Year 32 (34)
E\t'r lndoor
65 (68)
Body lndu
<25 70 (73)
25 to lO 25(26)
JO+-
6 (6)
M (SE)
Age
21 . 11 (53)
Protection
19.53 (.52)
Indoor hnnlng
# Ltlt!ume K3 15 (10)
Age Started
16.98 (.48)
#Last Year
24.20(3. 111)
#Per Month If Warm
6.90 ( 1.22)
t/ Per Month If Cool 8.0!! (1 27)
Hn per \\>eel.
uobathing 7.50 (.58)
Hn per \\cek lncldenlal II 33 ( 1.31)
Lifet ime Burn\ 2.29 ( 39)
Burns Ln t \'ear
L60 ( 14)
Day\ Smoked of last 30 day, 6.38 ( 95)
I# Cigarette per Oa)
2.42 (.59}
Day Aerobic\
2.43 (.20)
Day' nocrobic\ 2.02 (. 19)
ercd exploratory and hypothesis generat-
ing. Therefore, it 1s possible that the
nonsigmficant findings in the regression
analyses may not necessarily represent
true negative findings but merely effects
that we did not have the power to detect.
RESULTS
Descriptive Characteristics
Participants were 400 individuals, 79%
Am J Health Behav."" 2008;32(5):451-464
:\ot Dependt>nl
%(n)
P-ulut'
73.5 (294)
14 {217)
NS
79 (232)
NS
59 (173)
NS
59 (172)
< 0001
.0015
13 (37)
14 (J2)
15 (43)
23 C6H)
27 (79)
8 (24)
20 (59)
.0142
29 (85)
< 0001

63 (ItO)
22 (64)
15 (45)
\ 1 (Sl)
P-\alue
20.92 (.32> NS
23.47 (.31)
< 0001
35.93 (9)
.0009
17.47 (.43)
NS
5.75 (2.83)
< 0001
87 ( 1.09)
0003
2.35 (1.14)
.0010
2.44 (.35)
.0001
9.84 ( 79)
NS
I.R6 (.23)
NS
.67 (01!) <.0001
3.89 (.57) .0250
I 40 ( 35}
NS
2 06( 12)
NS
I 56 (II)
.0360
(n '" 316) of whom were Psychology 10 1
students and 21% (n 84) of whom were
other members of the university commu-
nity. Seventy-five percent (n 300) of the
sample was female, and the mean age of
participants was 21 years (SO 5.42}.
Sixty percent (n .. 240) of the sample were
first-year students, 25% (n 1 00) were
upper-class students, 8% (n 32) were
graduate or special students, and 7% (n
455
Tanning Dependence
Table 2
De mographi c Predictors of Tanning Dependence (n=397)
Variable OR
Fc!male 1.37
I rcshman Reference
Sophomore 0.97
Jun1or
0 78
Scmor/Other Grade 0.54
Afncan American Reference
Asian American I 93
\V hitc 7.60
Hispamc/Latino 5 50
Other Racc/Elhnicity 0 69
Skin rype I Reference
Skin Type II I 39
Skin Type lJ1 3.51
Skin T)pe rv 3.08
Skin Type\ 4.06
Sktn Jyp;;; VI 1.40
Psychology Student 0.60
28) were not in school. SlXty-six percent
(n - 264) of part1cipants were white, 17%
(n = 68) were African American, 11% (n =
44) were Asian American, and 6% (n = 24)
were other races/ ethnicitJes or multira-
cial/ethnic. Table 1 includes participant
characteristics by TO status.
The Cronbach alpha for the mCAGE
was .57 and for the mOSM-IV-TR was .56,
both of which are relatively low but reflect
the diversity of behaviors assessed by the
instruments and their brevity. Further
reliability testing and/ or modifications of
the measures should be conducted m
future studies. The mean of the mCAGE
scores was 0.47 (SO= 0.84) out of 4. and
the mean of the m S M ~ I V TR scores was
l 51 (SO = 1.31) out of 7. Based on the
mCAGE criteria, a small minority of the
sample ( 11%, n = 44) was identified as
tanning dependent. The most commonly
endorsed item referred to being annoyed
with people's advice against tanning ( 17%,
n = 68). mDSM-IV-TR criteria identified
93 (23% of the sample) tanning-depen-
dent individuals. The most commonly
endorsed item had to do with tanning
despite cancer awareness (45%. n = 178).
The measures successfully agreed in
456
P-\alue 95%CJ
0.28 (0.7R, 2.40)
0.94 (0.47. 2.01)
0.63 (0.28. 2 19)
0.22 (0.20, 1.44)
0.33 (0.52, 7 18)
0.00 (2.49, 23. 19)
0.06 (0.96, 31.59)
0.75 (0 07. 6.83)
0.55 (0.48. 3 99)
0.01 ( 1.35, 9. 12)
0.02 (l.21, 7.83)
0.01 (1.49, 11.04)
0.79 (O. n. 15.42>
0.28 (0.24, 1.51)
classifying 80% (n = 320) of the partici
pants: 294 (73%) as not tanning depen
dent. and 30 (7.5%) as tanning dependent.
Seventy-seven ( 19%) participants were
identified as tanning dependent by only
one of the 2 scales, either the mCAGE or
the mOSM-IV-TR. Because it is not yet
clear which scale measures TO more
accurately and due to the relatively low
hit rate, TO was defined for th1s study as
meeting criteria on either the mCAGE or
the mOSM-IV-TR. The foJlowmg analyses
compare TDs (n = 1 06, 26.5%) with non
TDs (n = 294, 73.5%) on a variety of
characteristics and behaviors.
Demographics
The following variables were entered
into the demographic logistic regression
model predicting TO: gender, ethnicity,
year in school, Fitzpatrick skin type, and
psychology student or not (Table 2). Signifi-
cant independent predictors of TO were
ethnicity and skin type. As expected, whites
had 7.60 times greater odds of being TO
compared to African Americans (95% CI =
2.49-23.19) conditional on other covariates
in the model. Thirty-four percent (n = 90) of
whites, 7% (n = 5) of African Americans,
and 16% (n = 1 1) of other races I ethnicities
Heckman et al
Table 3
UVR-Related Predictors of Tanning Dependence (n=387)
Variable OR P-vulue 95%CI
Lateume Lo'' R..Jerence
Moderate 144 0.31 (0.72. 2.91)
Ltfcume sunburns- Htgh 1. 15 0.72 (0.53. 2.47)
Burnt> Last Year I ow Reference
\ cur - \1oderatc 1.98 0.07 (0.95, 4. 14)
Burn' I\ ear lligh 2.85 0.01 ( 1.37, 5 91 )
I lour ... \\'cck lm:adcntal L O\\ Reference
Hour ... Week lnctdental E:11po.,.ure Moderate 1.27 0.54 (0.59. ?. 7'\}
lloUI'li'Wcck Incidental Exposure High 1.37 0.40 (0.66. 2.88)
Hours. Week Sunbathing Lo'' Rcterence
ll oul"\ \\ eek Moderate 2.32 0.06 (0.98, 5.50)
llour Week Sunbathing Uigh 7.54 0.00 (3.34, 17.02)
,\n} sunlel>' tanner tn pa ... t }car 1.21 0.59 (0.61 "'40)
l. i feu me mdoor tanmng exposure- one Reference
l 1 fcttme mdoor wnmng expo .. ure Moderate 059 0.33 (0.20, I 71)
Ltli:ttme mdoor wnnmg e\po,urc lligh 0.79 0.74 (0. 19. 3.151
Indoor tannmg tn last )ear- Reference
Indoor tannmg m last year Moderate 2.15 0.18 (0.70. 6 65)
Indoor tannmg m last year lltgh 1.73 0.40 (0.49. 6 13)
Indoor tanning In warm \\'Cather 2.99 0.03 ( 1.14. 7.82)
Indoor tannmg tn cool '"eathcr 1.57 0.34 (0.62. 3.951
Sun protet.ti\C beha\tor- Lo\\ Reference
protecth e beha\ lor - \loderatl'
Sun protecth l' behavior - I flgh
were classified as TD. Additionally, indi -
viduals with moderate skin types were
more likely to be TD than those with the
fairest or darkest skin types with ORs
ro.nging from 3.08 to 4.06 in the model for
Fitzpatnck skin types 3 through 5 com-
pared to the frurest skin type (skin type I) .
TD rates were 16% (n .. 7) for Type I's, 21',
(n 11) for Type IJ's, 39% (n - 28) for Type
Ill 's, 32% (n a 31) for Type IV's, (n 28)
for fype V's, and 4to (n 1) for Type VI's.
Surprisingly, gender was not a significant
independent predictor of TD status.
Exposure and Protective Behavior
The following variables were entend
into the UVR logtstic regression model
predtcting T D time spent sunbathing,
mcidental sun exposure, sunburns. in-
door tanning, sunless tanners, and pro
Am J Health Behav.n. 2008;32(5):451-464
0.27 0.00 (0.13. 0.55)
03 6 0.01 (0. 17. 0.74)
tecttve behaviors (Table 3). Significant
independent predictors of TD were hours
per week spent sunbathing in the sum-
mer, sunburns during the last year, in-
door tanning dunng warm weather. and
protective behaviors. Participants spent
a mean of 3. 77 (SD - 6.34) hours per week
tanntng in the summer. As expected,
those with the highest levels of summer
sunbathing had 7.54 (95% cr .. 3.34-17.02)
greater odds of bemg TD than did those
with the lowest levels conditiOnal on other
covariates in the model. Participants re-
ported a mean of 0.92 (SD 1.46) sunburn
during the last year. Those with the high-
est number of sunburns had 2.85 (95% Cl
"" 1.37 5.91) greater odds of being TD in
the model compared with those with the
fewegt sunburns. The mean score on the
protective behaviors scale was 22.41 out
457
Tanning Dependence
Figure 1
Odds Ratio of Being Tanning Dependent Relative to Baseline
Note.
0
...,
0
N
0
Point Estimate
Pointwise 95% Cl
Null Effect
Data Polrds
, .... ,,
I '
I '
I ',
II .. ____ .,.. ......
I
,
I
' I
'
'
I
'
I
'
I
I
I
I
I
I
I
I f
,' /
, ' '
," ,,"
I
vu:.: :.::;;::,:;::;;.::.: .,. .-..... ,_,,,,,, ........... .
2 5 10 20
HoltS per Week Slllbathing
50 10 15
I
I
I
I
I
I
'
'
'
I
I
' I
I
I
I
I
,
,
,
..... , .. _,,
""- .... ,.,,
20 25 30 35
Protecllon Score
Baselint- Is no time spent sunbathing and the lowest sun protection score, from Lhe model in which
tbe 2 variables were rncluded as restricted cubic splines. The effects relative to baseline are
significant where the confidence intervals do not cross I. The distribution of the dala Is
depicted by the bars on the bottom of the chart; ror ease of display, 1he bars were slightly j ittered
because of overlap.
of 35 (SO 5.52), suggesting moderate
levels of skin protection. As expected,
those who protected themselves from sun
exposure were less likely to be TD in the
model with ORs of 0.27 (95% CI = 0.13-
0.56) and 0.36 (95% CI .. 0.17-0.74) among
the moderate and high protectors, re-
spectively.
Figure 1 displays the impact of hours
per week sunbathing and sun protective
score on the odds of being classified as
tanning dependent conditional on the
other variables in the model. The odds of
being tanning dependent, compared to
those who do not spend any time sunbath-
mg increases as the hours per week
spent sunbathing, increases except at
very high levels in which little tanning
dependence was found. Because of sparse
data, the 95% confidence interval at the
highest levels becomes very wide, how-
ever, reflecting high uncertainty in the
458
point estimates at the highest level. The
relationship of sun protective behavior
with the odds of being tanning dependent
is more consistent as protective behavior
increases. Relative to those who have the
least protective behavior, those with more
sun protective behavior are less likely to
be tanning dependent.
Thirty-eight percent (n = 152) of the
sample had tanned indoors, and only 23%
(n = 92) of the sample had used sunless
tanners during the last year. The mean
age of tanning booth initiation was 17.26
years (SD = 3.91). The mean number of
lifetime tanning booth uses was 56.74
(SO = 87.99) . It is important to note that
the mean age of participants was 21 , so
the typical participant had used a tanning
booth 14 times per year during the past 4
years since age 1 7. Those who tanned
indoors during warm weather had 3.39
times the odds of being TD compared to
Heckman et al
Table 4
Other Health Behavioral Predictors of Tanning Dependence (n=393,
\'ar lnble OR
Ne\ crregularsmokcr Rcten . .-nce
m past I 14
Current smoker 1.81
J\naeroll1c exercise Low Reference
Anacmbic e"tercsc Modcnuc: 1.25
Anacroo1c 1-1 1gh 150
1\crohu: cxerc1sc Low Reference
Aerob1e cxcrc1se Moderate 1.83
Aerob1c exerctse -lligh 1.26
lln\i to Normal We1gltt. BMI <25 Rclerence
Overnctght. BMI > 25 and BMI<.. 'O I 03
Obe e, 8\fi>=JO 0.34
those who did not (95% CI 1.338.64),
conditional on other covariates m the
model. Surprisingly. use of chemical
sunless tanners and overall rates of in-
door tanning did not predict TO.
Other Health-Related Behaviors
The following vunables were entered
into the olher health behaviors logtstic
regression model predictjng TD; smokmg
status, body mass mdex (BMI) group, aero-
bic exercising. and anaerobic exerctsmg
(Table 4). Twenty-five percent (n 100) of
the sample reported having been a regu-
lar smoker at some point in time, and
23% (n 93) reported smoking during the
past month. Those who were current
smokers had greater odds of being TO
compared to those who had never smoked
(OR I 81, 95% CI 1.10 2 98). The mean
body mass index (BMI) of the sample was
24.63 (SO = 5.23), which is in the healthy
range. ln lhe model, those who were obese
(BM1> .. 30) were less likely to be TO than
those who were underweight or normal
weight (BMI<25), OR 0 34 (95% Cl 0.14-
0.85). Sixty four percent (n"'258) of the
sample was underweight or normal weight
(BM1<25), 23% (n 93) overweight
(BMI>25 and BMI<30), and 13% (n 51)
obese (BMI>=30). The mean number of
days per week spent doing aerobic exer-
cise was 2.16 (SO 2 06). and the mean
number of days spent doing strengthen-
ing exercises was 1.68 (SO "" 1.94).
Am J Health Behav."'
p.,aJue
0.!10 (O.P 3 01)
11.02 ( 1.10, 2.98)
0.4X (0.!\7, 2.35)
0 25 (0 l.021
0.07 (O.<JS, 3 . .54)
0.54 (0.60, 2.63)
() 42.
(0SY,I .78)
11.02 (0. J 4, 0.85)
Sensitivity analyses were also con-
ducted in order to assess whether chang-
ing the cut-points of the CAGE and DSM-
TV-TR scales used to define TO would
change our inferences. Tightening and
loosenang the criteria for TO did not change
the general inferences compared to the
original criteria, although some variables
did become less statistically significant.
The one major exception was the rela-
tionship of indoor tanning in warm
weather w1th tanning dependence. With
stricter critcna for TO, the point estt-
mate of indoor tanning in warm weather
was protective, whereas it was a risk
factor w1th a looser defimtion. This rela-
tionship should be examined more closely
in future studies.
DISCUSSION
These data demonstrated several pre-
dictors of tanning dependence, but some
measurement issues still need to be ad-
dressed. TO was predicted by ethnicity
and skm type, lack of skin protective
behaviors, and outdoor ond indoor tan-
ning behoviors among young adults, ns
well as smoking and body mass index.
These findings may offer new avenues for
research as well as skin protection and
skin cancer prevention interventions.
However, the internal reliability of the
measures was relatively low, and future
research should include more in-depth
psychometric development and analyses
459
Tanning Dependence
such as test-retest reliabilitY or factor
analysis. -
The current study found shghtly less
than half the rates ofTD as m the Warthan
ct nll7 study, and both studies obtained
higher TO rates on the mDSM IV-TR than
the mCAGE. Using the same sconng sys-
tem, 11% of the current participants scored
tanning dependent on the mCAGE (ver-
sus 26% in Warthan et all7), and 23%
scored dependent on the mDSM-IV-TR
fversus 53% m Warthan et al
11
). The pro-
portion meeting the CAGE criterion is
very stmilar to the 12% found by Poorsattar
and Hornung
28
in their sample of Seattle
undergraduates. These rates are also
similar to undergraduates' meettng CAGE
critena for alcohol (18%) and tobacco use
( 16%) ~ ~ The higher rates observed by
Warthan et al
17
make sense given that
their sample was recruited directly from
a beach as opposed to sampling from a
general population. TO rates would also
be likely to vary based on age, with older
individuals being less at risk due to lower
rates of tanning in general. ss
56
It was
interesting that TO did not vary by gender
as in the Warthan et aJI study. Women
were overrepresented tn the current
sample, so it may be that men who were
not particularly interested in tanning did
not choose to partictpate in this study
In the current study, TO was related to
racefethnicity and Fitzpatrick
44
skin type.
As expected, whites were more likely
than nonwhites to be tanning dependent,
but nonwhites were also represented in
the TO group. It is interesting to note that
a few African Americans screened posi-
tive for TO. These tended to be lighter-
skinned indtviduals, but this trend was
not stgnlficnnt (probably due to the small
sample size of this group). Therefore, non-
whites should not be ignored in skin
protection efforts.
Regarding Fitzpatrici<44 skin type, Type
I and Type VI participants were least at
risk for TO. Dark individuals (ie, Type VI)
may not need to make an effort to tan or
do not perceive tanning as culturally ap-
propriate, and very fair individuals may
not be able to tan or refrain from tanning
because they are aware of their high risk
for burning and other skin damage. The
TO rates among Types V (26%) and VI (4%)
were somewhat surprising, but it is im-
portant to note that Fitzpatrick skin type
was self reported. Therefore, some indi-
viduals may have rated their tanned skin
460
rather than their natural skin color or
minimized their risk for burning. This is
suggested by the lifetime use of tanning
booths by 57% of Types V and VI
As expected, TO was assoctated with
sun tanning, tanning booth use sun-
bums, and lower likelihood of protecting
the skin. These constructs are some-
what overlappmg, but the findings still
support the construct validity of the mea-
sures. A lack of association would rn1se
serious valtdity concerns. The amount of
intentional sun tanning was relauvely
low; however, the amount of incidental
exposure was high and widespread. Inter-
estingly, sun tanning appeared to be more
closely related to TO than indoor tanning,
which was only related during warm
weather. It was not known a priori whether
chemical sunless tarmer use would be
associated with TO or not. os sunless
tanner use could be viewed as a protec-
tive behavior or as a UVR tanning en-
hancer. Sunless tanning was associated
with TO in univariate analysis but was
not as strongly related to TO as the other
variables included in the multivariable
model (Tables I and 3). However, sunless
tanners could be recommended as an
alternative to UVR tanning, particularly
for TDs. An overwhelming majority of
studies have demonstrated UVR to be
harmful to the skin, but very few have
found sunless tanners to be dangerous.S7
The finding that almost 40% of the
sample had used tarming booths IS alarm-
ing, particularly when considering that
the mean age of the partictpants was 21,
the mean age of initiation was l 7, and the
mean number of lifetime uses was 57.
Tanning booth mitiation at age I 7 ts prob-
ably notable given that it likely corre
sponds with the high school prom ~ c a s o n
or spring break trips. An ideal prevention
opportunity may thus occur at a high school
just before prom time or spring break. A
previous study of 1275 adolescents found
an average age of initiation of 15 years;
however, that was a randomized house-
hold survey of teens from Boston and Min-
neapolisSt. Paul. 2 northern locnles with
cold climates.
25
Participants in the current
study were more likely to use tanning
booths during cold than warm weather.
That the risk for tanning booth use in-
creases during cold weather could be re-
Lated to greater difficulty sun tanning at
that time of year preparing for winter
vacations in warm locales. self-treatment
for seasonal affective disorder,2
1
and so on.
However in the current studv. TO was
more closely related to indoor tanning dur-
sng warm weather. Thig suggests that TOs
may be utilizing all possible means to tan
regardless of the time of year. These is-
sues should be studied further and inter-
ventions tmlorcd accordingly.
It was expected that TO would be asso-
ciated with other health-related vanables
such as smoking, weight, and exercise.
Because Demko et aJ2
1
found that sub-
stance use was related to indoor tanning,
it was hypothesized that tobacco use would
be related to TO. Smokers may be more
likely to be TO due to a similar addictive
process or because both of these behav-
iors are often viewed as image enhanc-
ing We expected low- to overage-weight
indl\nduals to be at greater risk for TO
than overweight or obese persons It is
likely that obese individuals are more
concerned about their weight than hav
ing tanned skin and may not feel comfort
able exposmg their bodies in the manner
necessary to receive high levels of UVR
We also expected that exercise would be
related to TO, but the direction of the
relationship was uncertnm. Demko et
a122 found that dieters wore more likely
to use tanning booths but that exercising
were less likely to do so. It would
make sense that dieters or exercisers
would tan more often because they are
concerned about their appearance or, al
ternatively, that dieters/exercisers may
tan less because they are concerned about
their health. '
2
:ZH&.s<J However. we found no
independent relationship between TO and
exercise. Overall, these results provide
evidence for conceptualizing tanning prc-
occupatlOn as an addiction but do not rule
out potential relationships to eating dis-
orders or other psychiatnc problems such
as obsessive-compulsive disorder.
There are st..veral ways in which the
mDSM-IV-TR scale could be made more
consistent w1th the original American
Psychiatric Association substance depen
dence A withdrawal syndrome
18 really not discussed in the modified
scale An item such as "Do you experience
Jlttcnness or nausea when you don't tan
for a while after a period of regular tan-
ning?" could be added One of the sub
stance dependence criteria is spending a
great deal of time in actlVitJes related to
the substance. It appears that Warthan ct
al'
0
arbitrarily decided to usc one or more
Am J Health Behav .TM 2008;32(5):451464
Heckman et al
days per week spent tanning to defme "a
great deal of time: but an uppropriate
amount remains an empirical question.
Finally, the item referring to missing
work due to sunburns seems to fit better
conceptually with the item referring to
m1sssng activities due to tanning, rather
than the items with which it is currently
grouped that all refer to the amount of
time spent tanning. Moreover, the cut
scores used for substances mav need to
be modified for tanning. For example, 26%
of individuals with skin Type V were found
to be tanning dependent in the current
sample. Because such dark-skinned in-
dividuals are typically not found to have
high tanning rates, TO may have been
overestimated. Moreover, the mDSM-IV-
TR and mCAGE agreed on 80% of the
classtfications, but the mOSM-IV-TR was
much more inclusive. Further psycho-
metric development could raise agree-
ment between the scales. Likewise, be
cause the items were onginally devel-
oped to assess substance use, more in-
depth testing of the items, such as cogni-
tiVe mterviewing, might help strengthen
their validity for use with tanners.
The popularity of conceptualizing ex-
cessive nonsubstance behaviors {food,
sex, gambhng, etc) as addictions has in-
creased in recent vears ' f Previous stud
ies have provided some support for con-
ceptualizing excessive tanning as an ad-
diction. Excessive tanning has been mea
sured using standard addiction mea
sures,
10
tanning has been found to be
associated with substance use,n tanners
find tanning physiologically reinforcing,
26
tanners have been concerned about quit-
ting tannmg
25
and have also demonstrated
physiologic withdrawal symptoms.
17
There
are certainly some similantics among
excessive tanning and traditional addic-
tions, suggesting possible biopsychosocial
links. It may be that many tanners are
first exposed incidentally to the sun dur-
ing childhood activities, then tan inten
tionally for primarily psychosocial rea-
sons such as appearance, relaxntion, or
socialtzation; and then a small subgroup
experiences a strong physiologic reaction
to tanning, which in some cases may be
related to an underlying addictive or mood
disorder. It ts important to note that not
all tanning behavior or even frequent
behavior should be seen as indicative of
TO. People tan for a variety of reasons,
and only a subset would meet criteria for
461
Tanning Dependence
TO including having tanning-related prob-
lems such as tolerance, withdrawal, and
other negative consequences. In addi-
tion, similarities could be drawn between
excessive tanning and obsessive-com-
pulsive disorders,
6
l eating disorders,
18
and
body dysmorphic disorder, S9 each of which
also has biopsychosocial components.
Which conceptualization is most useful
has not yet been determined.
Limitations of the current study in-
clude that it used a convenience sample,
is cross-sectional, and based on self-re-
port data. Tt is possible that the sample of
primarily Virginia psychology students is
not generalizable to some other popula-
tions. Due to the single administration of
the survey, it was not possible to monitor
changes in patterns of UVR exposure over
time. Additionally, all data were self-re-
port and did not measure actual time
spent tanning or skin damage levels.
However, because the survey was con-
ducted online, responses may have been
more truthful than an in-person inter-
Vlew in which demand characteristics
are greater. As the literature expands in
this area, future research should further
refine and validate measures of TO. For
example, objective measures of WR ex-
posure could be used (eg, spectrophotom-
etry). Other possible directions for future
research would be to further explore TO
prevalence in various populations. The
relationship between TO and other addic-
tive, eating, obsessive-compulsive disor-
ders should be investigated. For example,
TO could be compared with drugs other
than tobacco use. Researchers should
further explore tanning motivations and
tailor interventions accordingly. For ex-
ample, intervention studies might at-
tempt to intervene prior to age 17 and
focus on school-related events such as
prom and spring break in order to prevent
future TD. Ideally, interventions would
reduce the importance placed on appear-
ance in general and, specifically, the
unportance placed on tanning as an ap-
pearance enhancer.
Acknowledgments
The authors would like to thank Rick
Gibbons, Heike Mahler, John Roberts,
and Sharon Manne for their consultation
during this project.
REFERENCES
l.L.im HW, Gilchrest BA, Cooper KD, et al.
462
Sunlight, tanrung booths, and VItamin D. JAm
Acad Dennatol. 2005;52(5):868-876
2.ACS. What You Need to Know About Skin
Cancer. American Cancer Society 2006.
3. Robinson JK. Rigel OS, Amonette RA Trends
in sun exposure knowledge, atmudes, and
behaviors: 1986 to 1996. J Am Acad Dennatol.
1997;37(2 Pt 1): 179- 186.
4 Beasley TM, KnteJ BS. Factors that influence
health risk behaviors among tanning salon
patrons. Eva/ Health Prof 1997 ;20(4 ):371-388.
5.Ciarke VA, Williams T. Arthey S. Skin type
and optimistic bias in relation to the sun
protection and suntanning behaviors of young
adults. J Behav Med.. 1997;20(2):207-222.
6.Hoegb HJ, Davis 80, Manthe AF. Sun avoid-
ance practices among non-Hispanic white
Californians. Health Educ Behav.
1999;26(3):360-368.
7.Tunisi R, Hillhouse J, Gebert C. Examination
of cognitive variables relevant to sunbathing.
J Behau Med. 1998;21(3):299 313.
8.Hillhouse JJ, Stair AW. 3rd, Adler CM Pre-
dictors of sunbathing and sunscreen use in
college undergraduates. J Behav Med.
1996; 19(6):543-561
9.Jones JL, Leary MR. Effects of appearance
based admonitions against sun exposure on
tanning mtentlons tn young adults. Health
Psychol. 1994; 13(1):86-90.
IO.Leary MR, Jones JL. The" social psychology of
tanning and sunscreen use: self- presenta-
tional motives as a predictor of health nsk.
Journal of Applied Social Psychology.
1993;23: 1390-1406
11 Miller AG, Ashton WA, McHoskey JW, et al.
What price attractiveness? Stereotype and
risk factors m suntanning behavior. Journal of
Applaed Social Psychology. 1990;20: 1272 1300.
12.Borland R, Hill D, Noy S Being sunsmart:
Changes in community awareness and re-
ported behaviour foUowing a primary preven
tion program for skin cancer control Behau
Change. 1990;7:126-135.
13.Bullcr DB, Buller MK, Beach B, et al. Sunny
days, healthy ways: evaluation of a skin
cancer prevention curriculum for elementary
school-aged children. J Am Acad Dermatol.
1996:35{6):911-922.
14.Robinson JK. Behavior rnodificatJon obtained
by sun protection education coupled with
removal of a skin cancer. Arch Dermatol.
1990; 126(4):477-481.
lS.Rossi JS, Blais l..M, Weinstock MA. The
Rhode Island Sun Smart Projecl: skin cancer
prevention reaches the beaches Am J Pu.bltc
Health. 1994;84(4):672-674
16.Wemstock MA, Rosst JS. The Rhode Island
Sun Smart Project: a scientific approach to
skan cancer preven lion Clin Dermatol.
1998; 16(4);411-413.
17.Warthan MM, Uchida T, Wagner RF, Jr UV
light tanning as a type of substance-related
disorder. Arch Dermacol. 2005; 141(8):963-966.
18.BBC N. Young utanorex.ics" risking cancer
(online), Available Ill: http://news.bbc.co.uk/
go/ pr I fr / /1/hi/programmes/ real _stor-y 1
3737125/stm. Accessed Apnl 28, 2006.
19.Shapiro JJ .. Teena lead, adults follow m
sk1ppmg sunscreen (onhne), Ava1lable at:
www.cancer.org. Acctssed March 4, 2003.
20.Boldeman C, Jansson B, Oat H, et at. Sunbed
use among Swed1sh adolescents m the 1990s
a deehne w1th an unchanged relationship to
health nsk behaviors. &and J Public Health.
2003;31 (3):233-237.
21.H11lhouse J , Stapleton J, Tumsi R. Associa
t1on of frequent mdoor UV UJnning w1th
seasonal affective disorder. Arch Demtatol.
2005:141(11): 1465.
22.Demko CA, Borawsk1 EA, Oeba.nne SM, et al.
Use of mdoor tannmg facilities by wh1te
adolescents in the United Stotes. Arch Pediatr
Ado/esc Med 2003; I 57(9) 854 860
23.0'Riordon Dr.. F1eld AE, Geller AC. et al.
Frequent tnnning bed use, weight concerns,
and other health risk bchav1ors ln adolescent
females (Unated States) . Cancer Causes Control.
2006; 17(5) :679-686.
24. Boldeman C, Jansson B. Nilsson B, et al.
Sunbed use m Swed1sh urban adolescents
related to behaviornl chamctcnstlcs. Preu Med
1997;26(1) : 114119.
25.Zeller S, Lazov1ch 0, Forster J, et al. Do
adolescent mdoor tanners exhibit depen-
dency? J Am Arod Dcrmatol 2006;54(4):589
596.
26.Feldman SR, L1guon A, Kucenlc M, et al.
Ultravtolet exposure IS a rcmforcang stimulus
10 frequent mdoor umners. JAm Aood DermatoL
2004;5 I( 1) :4551
27.Kaur M, L1guon A, Lang W, et ul. lnductJOn of
wtthdrawalhke symptoms m a small random
tzed, controlled tnal of op101d blockade an
frequent tannen. J Am Acad Dermatol.
2006;54(4) :709-711.
28.Poorsaunr SP, Hornung RL. UV hght abuse
and h1gh rtsk tannmg behavior among under-
graduate college students. JAm Arod Dcrmatol.
2007;56(3):375 379.
PC, Carr DB, F'1sher JE, et al.
Plasma beta endorphin and betn- hpopro-
tein response to ult r nv1olet radiution. Lan
cet . 1983;2(8342): 166.
30.Belon PE. UVA exposure and p1tunory secre
rion. Vartations of human hpotropm concen
trations (beta LPH) after UVA exposue.
Photochem Photob1ol. 1985;42(3):327329.
3l.Gamblchler T, Bader A, Vojvodic M. et al .
Plasma levels of opi01d peptidcs after sunbed
exposures. Br J Dermatol 2002; 147(6): 1207-
1211.
32.Wmtzcn M, 0St!Jn OM, Poldennan MC, et al.
Total body exposure to ultraVlolet radiation
does not influence plasma levels of Immu-
noreactive beta-endorphin m m11n.
Photodcrmatol Photo1mntunol Pltotomed.
200 I ; 17(6) 256260
33.La.zovlch 0, Forster J , Sorensen G, et al .
Charoctenshcs associated wtlh use or mten-
Am J Health Behav.'"' 2008;32(5):451 464
Heckman et a1
uon to use indoor tanning among adolescents.
Arch Ped1atr Ado/esc Med 2004; 158(9). 918
924.
34.APA. Dtagnostlc and Stausticnl Manual of
Mental Disorders, Founh Ed1tJon, Text Revt
s1on Washington, DC: Amencan Psych1atnc
2000.
35.Ma\field D, McLeod G, Hall P. The CAGE
que"stionnatre: validation of a new alcoholism
screemng tn!>lrument. Am J Psychtatry.
1974; 131(10) : 1121- 1123.
36. Liskow B, Campbell J, Nickel E.J, et al
Val1d1ty of the CAGE quesuonnalre m scretn
ing for al cohol dependence m u walk-m
(tnage) chnac. J Srud Alcohol 1995;56(3):277-
281 .
37.Malet L, Schwan R, Doltssiron D, et nl
Valid1ty of the CAGE questionnaire tn hospl
tal. Eur Psychratry 2005;20(7):484489.
38.Bisson J, Nudeau L, Demers A The Vl\hdity of
the CAGE scale to scnen for heovy drinking
and drinking problems m a general popula
tion survey. AddKCron. 1999;94(5) :715722.
39 SCIDWebpage. Rehabllty nne! Vahdit.> of the
SCID l (online) . Avatlable et: http:/ /
cpmcnet.columbta.edti/ depl / e1d. Acceued
September 29. 2006.
40.Gtbbons FX. Gerrard M Pred1cung voung
adults' health nsk behavtor J P.:rs Soc PsyclwL
1995,69(3) :505 517.
41.Gtbbons FX, Gerrard M. A soc1al rcucuon
model of adolescent health risk In Suls J ,
Wallston K, (Eds). Socnll Foun-
dations of Health. Oxford, U. K .. Blackwell
2003.
42.Hlllhouse J, Tunis1 R, Hoh\'lSkt F, et al . An
exammatton of psychological vanables rei
evant to nrtlfic1al tannmg tendencres Journal
of Health Psychology 1999;4.507-516
43.Hillhouse JJ, Tumsr R, Kastner M. Modehng
tanmng salon behav1oral tendencies usmg
appearance motivation, selfmonuoring and
the theory of planned behrwi01 . 1-Jealch Educ
Res. 2000; 15(4):405 414.
44 Fitzpatrick TB. The vahd1tV nnd practicnhty
of sun-reactive skin types I through VI. Arch
Derma toT. 1988:1 24(6):869 871.
45.Gibbons FX, Gc."rrnrd M Health imnges and
the1r effects on heulth bchnv1or. In Gibbons
BBFX, (Ed) . Health, Copmg, und Well bemg:
Perspectives from Soc1al Companson Theory.
Mahwah, NJ: l.owrence Erlbaum Assoctatcs
1997:63-94
46.Gibbons FX. Gerrard M, Lane DJ, et nl. Usmg
UV photography to reduce use of tanning
booths. a test of cogmttvc medlatton Heulth
Psychology 2005,24(4)358 363
47.Maddock RC, Fulton RL. Mot1vauon. Emo-
uons, and Leadersh1p: The S1lent S1de or
Management . Westport, CT: Quorum Books/
Greenwood Pubhshmg Group, Inc. 1998.
48,Wemstock MA, Ross1 JS, Reddmg CA, et Ill .
Sun protection behaviors and U\ges of change
for the pnmary prevention of skm cancers
among beachgoers m southeastern Ne\1. En-
461
Tanning Dependence
gland. Ann Behm Mcd. 2000:22(4):286293.
49.Mahler HI, Fitzpatnck B, Parker P, et aJ. The
relauve effects of a health-based versus an
appearance-based intervention des1gned to
ancrease sunscreen use. Am J Health Promot.
1997:11(6):426-429.
SO.Mahler HI, Kulik JA, Gibbons FX, et al.
Effects of appearance-based anterventions on
sun protection mtenuons and self-reponed
behaviors. Health Psycho/ 2003:22(2): 199-
209.
Sl.Mahler HI, Kulik JA. Harrell J, et al. Effects
of UV photographs, photoaging mformation,
and use of sunless tannmg louon on sun
protect1on behav1ors. Arch Dermatol.
2005; 141 (3):373-380.
52.CDC. Youth riak behnv1or surveillance: Na-
llonnl College Health Risk Behnv10r Survey-
Umted States, 1995. MMWR CDC SUrve1U SUmm.
1997;46(6): 156.
53.llarrell FE. Regression Modeling
New York: Springer 200 I.
54 .Cohen J. A power pnmer. Psychol Bull.
1992;112(1):155-159.
SS.Boldeman C, Branstrom R. Dal H, et al.
Tannmg habits and sunburn in a Swedish
populatiOn age 1350 years. Eur J Cancer.
200 I :37( 18):244 1-2448.
464
56.Melia J, Bulman A. Sunburn and tanning in
a British populnuon. J Public Health Med.
1995: 17(2):223-229.
57.Petersen AD, Wu1f HC, Gmadeck1 R, et al.
Dihydroxyacetone, the ocuvc browmng ingre-
dient in sunless tannmg louons, mduces
DNA damage, cell-cycle block and apoptosis
in cultured HaCaT keratmocytes Murat Res.
2004;560(2): 173-186.
58.Greene K, Brmn LS. Messages lnfluencmg
college women's tannmg bed use: stahshcnl
versus narrat1ve <"vidence format and a self
asse!lsment to mcreaKe pcrcewcd susceptibil-
ity. J Health Commun. 2003;8(5):443-461.
59.Philhps KA, Conroy M, Oufrc!lne RG, et al.
Tanning m body dysmorph1c dtsorder.
Psychiatr Q 2006;77(2):129-138.
60.Buckley PF. Brown ES. Prevulence and con
sequences of dual diagnosis. J Clm Psyclltatry.
2006;67(7) cO I
61 Marun PR Petrv NM. Are non-substance
related addtct1ons really addictions? Am J
Addrct. 2005; 14( 1): 1-7.
62.Lean MR. Snltzmnn JL, Georgeson JC. Ap-
pearance motivattOn, obsessive-compulsive
tendenctes and cxcess1ve suntanning in a
communuy sample. J 1/ealth Psycllal.
1997;2(4):493499.
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REPORTS
I
UV light abuse and high-risk tanning behavior
among undergraduate college students
Solmaz P. Poorsattar, BS,a,b and Robin L. Hornung, MD, MPHb,c
San Francisco, California, and Seattle, Washington
Background: The failure of skin cancer prevention efforts to alter tanning behaviors may be a result of the
addictive nature of UV light.
Objective: This study attempts to determine the prevalence of UV light substance-related disorder (SRD).
Methods: A survey was administered to undergraduate college students. The cut down, annoyed, guilty,
eye-opener questionnaire was used to determine existence of SRD.
Results: Of 385 respondents, 12o/o scored posi tively on the cut down, annoyed, guilty, eye-opener
indicating SRD. Women, indoor tanners, students with tanning family and friends, and frequent ta nners
were significantly more likely than their peers to score positively.
Limitations: The small size is a li mitation of this study as results may not be generalizable to larger
populations. There also may be self-report bias.
Conclusimzs: A significant proportion of college students clemonsmtte evidence of SRD with respect to UV
light. (] Am Acacl Dermatol 2007;56:375-9.)
I
n the United States, the incidence of malignant
melanoma increases each year. l.
2
Research ex-
ploring the cause of this epidemic consistently
links excessive UV light exposure early in life to skin
cancer later in life
3
-
7
and finds young skin to be
part icularly sensitive to UV radiation.s-
11
Therefore,
decreasing UV light exposure during childhood and
adolescence is a central objective of skin cancer
primary prevention effo1ts.
Most prevention programs focus on educati onal
interventions meant to increase parents' and chil-
dren's knowledge of the dangers of UV light over-
exposure. Unfortunately, studies have shown that
From the University of California, San Francisco, School of
Medicine; Children' s Hospital and Regional Medical Center,
Seattleb; and Division of Dermatology, Department of Pediatrics,
University of Washington School of Medicine.c
Funding sources: None.
Conflicts of interest: None identified.
Accepted for publ ication August 26, 2006.
Reprint requests: Robin L. Hornung, MD, MPH, Division of
Dermatology, M2-7, Children's Hospital and Regional Medical
Center, 4800 Sandpoint Way NE, Seattle, WA 98105. E-mail:
robin.hornung@seattlechildrens.org.
Published online January 31, 2007.
0190-9622/ $32.00
2007 by t he American Academy of Dermatology, Inc.
doi:l 0.1 016/j.jaad.2006.08.064
increased knowledge, especially among adolescents
and young adults, often fails to alter tanning behav-
ior and attitudes.
12
-
19
It has been suggested anecdotall y for years that
one reason tanning is so popular is that UV light is
addictive.
20
-
2 2
Many adolescents who regularly tan
indoors self-report difficulty in quitt ing tanning
23
Experiments have also shown that UV light is
a reinforcing stimulus that causes endorphin re-
lease.
24
-
26
A recent study among beachgoers in Texas
confirmed that many sunbathers met criteria for
having substance-related disorder (SRD) witb respect
to UV light.
27
The potential addictive nature of UV
light tanning might explain why educati onal preven-
tion efforts have been largely unsuccessful.
To better understand the UV light tanning behav-
iors of adolescents and young adults and their
reasons for persistently tanning, this study examines
a population of college-age tanners, their tanning
attitudes and behaviors, and prevalence of SRD with
regard to UV light.
METHODS
After permission was obtained from our human
subj ect.<; review committee, students attending a
convenience sample of undergraduate classes in all
colleges of the University of Washington in Seattle
during December 2005 and j anuary 2006 were asked
375
376 Poorsattm and Hornung
Table I. Characteristics, self-reported tanning
practices, and cut down, annoyed, guilty,
eye-opener questionnaire responses of all
survey respondents and those scoring
positively on the questionnaire
Student characteristics
Female*
Skin phot ot ype
I
II
Il l
IV
v
Age, y
17 and 18
19and20
21 24
25-30
Family history of skin
cancer*
Yes
No
Unknown
Personal history of
skin cancer
Tanning pract ices
History of blistering
sunburn*
Outdoor tanners*
Indoor t anners*
Fami ly members tan*
Friends tan*
History of t anning
bed burn*
All Respondents
survey
respo ndents
(n = 375)
65%
19%
32%
28%
16%
4%
22%
49%
22%
7%
20%
65%
1 5o/o
Oo/o
48%
70%
33%
41%
83%
1 5o/o
All uv
scoring
pos iti\'e.ly on the
CAGE ( n = 46)
87%
11%
33%
35%
20%
2%
11 o/o
63%
22%
4%
35%
50%
1 5o/o
Oo/o
63%
1 OOo/o
76%
59%
1 OOo/o
57%
light Respondents scoring
tanners positively on th e
Modified CAGE questions (n 256) CAGE (n 46)
Have you ever felt you 21 o/o 87%
ought to cut down
on your tanni ng?
Have peopl e annoyed 9o/o 41%
you by criticizing
your tanni ng?
Have you ever felt bad 20% 87%
or guilty about your
tanning?
Have you ever thought 13% 28%
about tanni ng first
thing in the morni ng?
CAGE, Cut down, annoyed, guilty, eye-opener.
*P < .05 when comparing all survey respondents with t hose
scoring positively on t he CAGE.
J AM ACAD 0 ERMATOL
MARCH 2007
to complete a 1-page anonymous multiple-choice
questionnaire. Information coll ected incl uded de-
mographic data, personal tanning practices, and
tanning practices of family and friends.
Four questions in the survey also comprised
a modified cut down, annoyed, guilty, eye-opener
(CAGE) questionnaire tool, which was used to
determine whether patticipants showed symptoms
of SRD with regard to UV light (see Table I for
modifi ed CAGE questions). The CAGE questionnaire
is a thoroughly tested tool most often used to identify
SRD with regard to alcohol.
28
Other researchers have
suggested that screening for other substances can
effectively be incorporated into the CAGE format
by simply including references to them in the ques-
tions.
29
The CAGE questionnaire is reported to be
60o/o to 90o/o sensitive for detecting Sills when two or
more questions are positive and 40o/o to 60o/o specific
for excluding substance abuse.
30
Descriptive frequencies were used to describe
survey responses. The percentages reported for each
item are based on the valid number of responses to
the item. Students who reported experiencing two or
more of the CAGE criteria were considered as having
a positive screen result, denoting suggested SRD with
respect to UV light. lf students experienced none or
only one of the 4 criteria, they were assigned a
negative CAGE result. When comparing discrete var-
iables, Fisher's exact tests were performed to deter-
rnine statistical significance. The data were analyzed
using software (STATA 7.0, StataCorp LP, College
Station, Tex).
RESULTS
In all, 385 students participated (response rate =
90o/o). Of the 385 participants, 10 were older than 30
years and their responses were excluded from this
analysis. Only students who reported ever purposely
tanning were asked to complete the CAGE question-
naire. Demographics, relevant history, self-reported
tanning practices, and CAGE questionnaire re-
sponses are reported in Table I.
In this study, 76% of female students reponed
purposely tanning their skin versus 59o/o of male
students (P = .001). Of the female students, 42o/o
reported using indoor tanning devices versus 17% of
the male students (P = .000). Of students surveyed,
9% purposefully tanned their skin 20 or more times
per month.
Overall, 12% of the total sample, 18o/o of the self-
reporting suntanners, and 28o/o of indoor tanners
scored positively on the CAGE indicating SRD with
regard to UV light. Of the students who reported
purposely tanning their skin, 22o/o of female suntan-
ners had positive CAGE results, compared with 8o/o
) AM ACAD DRMATOL
VOLUME 56, NUMBER 3
Table II. Self-reported motivations for UV light tanning
Poorsattar and Hornung 377
AU lN light Respondents scoring Indoor tanning Initial motivation for
tanners positively on the device users indoor tanning
(n 240)
To look better 7S%
To relax 41%
To gain a protective base tan 34%
For special events 2S%
To feel healthy 22%
Social activity with friends 18%
Peer pressure 3%
Special price promotion 3%
Medical reasons 2%
Other (eg, work) 7%
CAGE, Cut down, annoyed, guilty, eye-opener.
of male suntanners (P = .007). Indoor tanning device
users were much more likely to be flagged as
potentially having a UV light disorder than nonusers
(28% vs 12%, P = .000). Students with friends and
family members who used indoor tanning macb.ines
were significantly more likely than students without
such fri ends and family to test positive (P = .000 and
P = .016, respectively). The likelihood of scoring
positively on the CAGE increased as reported fre-
quency of tanning increased.
The reasons respondents gave for tanning are
reported in Table II.
First indoor tanning experience
Of respondents, 66% repott ing ever using an
indoor tanning device were also current users
(have used one within the last year). Of students
reporting ever using an indoor tanning device, 49%
had received a burn from indoor tanning device use,
and 79% of these previously burned students still
currentiy tanned indoors. The mean age of first using
a tanning device was 16.8 years, and the range was
7 to 23 years. Of indoor tanners, 87 (71 %) started
before the age of 18 years and 12 (10%) at the age
of 14 years or younger.
In all , 59% reported going to an indoor tanning
salon for the first time with friends, 18% went alone,
14% went with their parents, and 11% with their
siblings. Reasons respondents gave for using an indoor
tanning device their fi rst time are given in Table II.
DISCUSSION
In all, 18% of undergraduate students who admit-
ted to purposely tanning their skin scored positively
on the CAGE questionnaire, indicating probable
existence of SRD with respect to UV light. This
number is significant and comparable with the 18%
of drinking college students who scored positively
on the CAGE questionnaire with respect to alcohol in
CAGE ( n 43) (o 112) (n 124)
91% 82% 60%
47% 44% 14%
44% 41% 19%
44% 46% 40%
30% 29% 8%
21% 20% 11 o/o
9% 4% 10%
9% 8% 10%
S% 4% 0%
Oo/o 7% 2%
a Midwest study
31
and the 16% of college students
who reported smoking cigarettes daily in a 2002
National Inst.it.utes of Health study.
32
Many of our respondents also exhibited high-risk
tanning behavior and had experienced a bad or
blistering burn from the sun and indoor tanning
devices. Of students sutveyed, 9% purposefully tanned
their skin 20 or more times per month. The tendency
to sunburn, lifetime number of severe sunburns, and
cumulative UV light exposure are all positively asso-
ciated with risk of developing future skin c.ancer.
33
In
addition, our study shows a strong positive correlation
between high-risk tanning behavior and SRD with
respect to UV light. Significantly more students scoring
positively on the CAGE questionnaire bad experi-
enced a bad or blistering sunburn (63%) and many
more of these students who were also indoor tanners
had received a burn from an indoor tanning device
(57%). Of students with SRD, 16% pL11]10Sefully tanned
their skin 20 or more times per month.
Students with a known family history of skin
cancer are also at much greater risk of developing
cancer
4
and surprisingly are significantly more likely
to tan their skin than those without a family history
of skin cancer. Of students with a positive family
history, 77% purposely tanned their skin outdoors
and 45o/o of them used indoor tanning devices. This
finding is consistent with a previous study that found
Midwestern college students with a positive family
history of skin cancer were 1.5 ti mes more likely to
use tanning lamps than those wi thout
1 9
Personal
experi ence apparentl y fails to alter tanning behavior.
The association found in previous studies between
frequent indoor tanners and tobacco and other
substance abuse also suggests that individuals who
tan frequently may be susceptible to multiple addic-
tive disorders.
34
-
36
Almost half of tanning students rep01t tanning
to relax, which is a strong motivating factor that has
378 Poorsattm and Hornung
been noted by numerous previous studies.
13

19

37

38
As expected of an addictive practice, established
users in our study reported tanning to relax and to
feel healthy much more often than first-time users
(44% vs 14%). Furthermore, it has been shown that
adolescents who agree that tanning improves their
mood are more likely to self-report difficulty in
quitting tanning.
23
As previously discussed, education alone will
probably not stop high-risk tanning behavior.
Numerous studies examining other health behavior
changes, particularly those of addictive behaviors,
have shown that successful self-changers use differ-
ent processes at each parti cular stage of change.
39

40
Future interventions should take into consideration
the behavioral stage and moti vational readiness of
each individual to change problem tanning behavior.
In addition, if, in fact, tanning is addictive, the
argument to prohibit the use of indoor tanning
devices by minors, as recommended by the World
Health Organization,
41
is strengthened.
There are several limitations to our study. The
sample size was small as was the group identified
as positive for SRD. The behaviors of undergraduate
college students at this university may not be able
to be generalized over all undergraduate students or
the general population. Students self-reported their
tanning behavior and medical history, which is a
potential subjective limitation. Some student respon-
dents may have answered the CAGE items with less
accuracy because of social desirability concerns.
CONCLUSION
The prevalence of SRD with respect to UV light
among college tanners helps explain why it has
been particularly difficult to modify high-risk tan-
ning behavior in adolescents and young adults. The
existence of this SRD should strengthen arguments to
increase regulations on the indoor tanning industry
and further justify following in the lead of public
health efforts that have successfull y decreased use
of other addictive carcinogens.
We would like to thank Courtney McNamara and Dylan
Mart for their help with data collection, and Do Peterson,
MS, for reviewing our survey tool and study design.
REFERENCES
1. Thompson JF, Scolyer RA, Kefford RF. Cutaneous melanoma.
lancet 2005;365:687-701.
2. Beddingfield FC Ill. The melanoma epidemic: res ipsa loquitur.
Oncologist 2003;8:459-65.
3. Green A. Sun exposure and the risk of melanoma. Australas
J Dermat ol 1984;25:99-1 02.
4. Holman CDJ, Armst rong BK. Pigmentary traits, ethnic origin,
benign nevi, and family history as risk factors for cutaneous
melanoma. J Natl Cancer lnst 1984;72:257-66.
J AM ACAD 0 ERMATOL
MARCH 2007
5. Spencer JM, Amonette R. Tanni ng beds and skin cancer:
artificial sun + old sol = real risk. Clin Dermatol1998;16:487-501 .
6. Holman CDJ, Armstrong BK. Relationship of cutaneous malig-
nant melanoma to individual sunlight exposure habits. J Natl
Cancer lnst 1986;76:403-14.
7. Zanetti R, Franceschi S, Rosso S, Colonna 5, Bidoli E. Cut aneous
melanoma and sunburns in childhood in a southern European
population. Eur J Cancer 1992;28A:1172-6.
8. Stern RS, Weinstein MC, Baker SG. Risk reduct ion for non-
melanoma skin cancer with childhood sunscreen use. Arch
Dermat ol 1986;122:537-45.
9. Council on Scientific Affairs. Harmful effects of ult raviolet
radiation. JAMA 1989;262:380-4.
10. Walter SO, Marrett LD, Shannon HS, Roy P. The associat ion of
cutaneous malignant melanoma with the use of sun beds and
sunlamps. Am J Epidemiol1990;131:232-43.
11. Levine JA, Sorace M, Spencer J, Siegel OM. The indoor UV
tanning indust ry: a review of skin cancer risk, health benefit
claims, and regulat ion. J Am Acad Dermatol 2005;53:
1038-44.
12. Monfrecola G, Fabbrocini G, Posteraro G, Pini D. What do
young people t hink about the dangers of sunbathi ng, skin
cancer and sunbeds? A quest ionnaire survey among Italians.
Photodermatol Photoimmunol Photomed 2000;16:15-8.
13. Mawn VB, Fleischer AB Jr. A survey of attitudes, beliefs, and
behavior regarding tanning bed use, sunbathing, and sun-
screen use. J Am Acad Dermat ol 1993;29:959-62.
14. Arthey S, Clarke V. Suntanning and sun protection: a review
of the psychological literature. Soc Sci Med 1995;40:265-74.
15. Robinson JK, Rademaker AW, Sylvester JA, Cook B. Summer
sun exposure: knowledge, attitudes, and behaviors of midwest
adolescents. Prev Med 1997;26:364-74.
16. Gell er AC, Colditz G, Oliveria S, Emmons K, Jorgensen C, Aweh
GN, et al. Use of sunscreen, sunburning rates, and tanning bed
use among more than 10,000 US children and adolescents.
Pediatrics 2002;1 09:1009-14.
17. Robinson JK. Rigel OS, Amonett e RA. Trends in sun exposure
knowledge, attitudes, and behaviors: 1986 to 1996. J Am Acad
Dermat ol 1996;347:179-86.
18. Benjes LS, Brooks DR, Zhang Z, Livstone L, Sayers L, Powers C,
et al. Changing patterns of sun protection between t he first
and second summers for very young children. Arch Dermatol
2004;140:925-30.
19. Knight JM, Kirincich AN, Farmer ER, Hood AF. Awareness of the
risks of t anning lamps does not influence behavior among
college students. Arch Dermat ol 2002;138:1 311 -5.
20. Netburn D. Young, carefree, and hooked on sunlamps. New
York Times May 26, 2002;9.
21. Chedru MF, Dumont C, Jourdain F, Postel-vinay N, Dab W.
Cutaneous melanoma prevention: modify behaviors [in
French]. Rev Prat 2004;54:1165-6.
22. WCCO-TV. Hooked on tanning? Available from: URL:http://
www.wcco.com/specialreports/local_story _052181257.html.
Accessed July 3, 2006.
23. Zeller S, Lazovich D, Forster J, Widome R. Do adolescent
indoor tanners exhibit dependency? J Am Acad Dermatol
2006;54:589-96.
24. Feldman SR. Liguori A, Kucenic M, Rapp SR, Fleischer AB Jr,
Lang W, et al. Ultraviolet exposure is a reinforcing st imul us in
f requent indoor tanners. J Am Acad Dermatol 2004;51 :45-51.
25. Levins PC, Carr DB, Fi scher JE, Momtaz K. Parrish JA. Plasma
beta-endorphin and beta-lipot ropin response t o ultraviolet
radiation. Lancet 1983;2:166.
26. Belon PE. UVA exposure and pituitary secretion: variat ions of
human lipotropin concentrations (j3LPH) after UVA exposure.
Photochem Photobiol 1985;42:327-9.
) AM ACAD DRMATOL
VOLUME 56, NUMBER 3
27. Warthan MM, Uchida T, Wagner RF Jr. UV light tanning as a type
of substance-related disorder. Arch Dermatol2005;141:963-6.
28. Ewing JA. Detecting alcoholism: the CAGE questionnaire.
JAMA 1984;252:1905-7.
29. Brown RL Identification and office management of alcohol
and drug disorders. In: Fleming MF, Barry KL, editors. Addictive
disorders. StLouis: Mosby; 1992. p. 28.
30. Mersy OJ. Recognition of alcohol and substance abuse. Am
Fam Physician 2003;67:1 529-32.
31. Boyd U, McCabe SE, d' Arcy H. A modified version of the CAGE
as an indicator of alcohol abuse and its consequences among
undergraduate drinkers. Subst Abuse 2003;24:221-32.
32. Johnston LD, O'Malley PM, Bachman JG. Monitoring the future
national survey results on drug use, 1975-2002. Volume II:
college students and adults ages 19-40 (National Institutes
of Health publication No. 03-5376). Bethesda (MD): National
Institute on Drug Abuse; 2003.
33. Abdulla FR, Feldman SR, Williford PM, Krawchuk D, Kaur M.
Tanning and skin cancer. Pediatr Dermatol 2005;22:501-12.
34. Demko CA, Borawski EA, Debanne SM, Cooper KD, Stange
KC. Use of indoor tanning facilities by white adolescents
Poorsattar and Hornung 379
in the United States. Arch Pediatr Adolesc Med 2003;157:
854-60.
35. Lazovich D, Forster J, Sorensen G, Emmons K, Stryker J,
Demierre MF, et al. Characteristics associated with use or
intention to use indoor tanning among adolescents. Arch
Pediatr Adolesc Med 2004;1 58:918-24.
36. Boldeman C, Jansson B, Nilsson B, Ullen H. Sunbed use in
Swedish urban adolescents related to behavioral characteris-
tics. Prev Med 1997;26:114-9.
37. Diffey BL. Use of UV-A sunbeds for cosmetic tanning. Br J
Dermatol 1986;1 15:67-76.
38. Dougherty MA, McDermott RJ, Hawkins MJ. A profile of
commercial tanning salons. Health Values 1988;12:21-9.
39. Prochaska JO, Velicer WF, Rossi J5, Goldstein MG, Marcus BH,
Rakowski W, et al. Stages of change and decisional balance for
12 problem behaviors. Health Psycho! 1994;13:39-46.
40. Prochaska JO, DiClemente CC, Norcross JC. In search of
how people change: applications to addictive behaviors. Am
Psycho! 1992;47:1102-14.
41. World Health Organization. Artificial tanning sunbeds-risks
and guidance. Geneva: World Health Organization; 2003.
4th International Workshop for the Study of Itch
San Francisco, California
September 9-11, 2007
Venue: Hilton San Francisco Financial Distti ct, 750 Kearny Street, San Francisco, California 94108
Phone: 415-433-6600; Fax: 415-765-7891; Web site:
http:/ / v.rwwl . hjl ton.com/ en_ US/ hi/hoteVSFO FDHF-Hilton-San-Francisco-Financial-District-
California/ index.do.
Meeting organizers and contact: Prof. Earl Carstens, M. Carstens, Uni versity of California, Davis,
Section of Neurobiology, Physiology, & Behavior, 1 Shields Ave, Davis, CA 95616. Phone: 530-752-
7767; Fax: 530-752-5582; E-mail: eecarstcns@ucclavis.eclu.
Official meeting Web site: http://itch2007sanfrancisco.ucdavis.edu/.
Calcium/Vitamin D Supplementation and
Cardiovascular Events
Judith Hsia, MD; Gerardo Heiss, MD, PhD; Hong Ren, MS; Matthew Allison, MD, MPH;
Nancy C. Dolan, MD; Philip Greenland, MD; Susan R. Heckbert, MD, PhD;
Karen C. Johnson, MD, MPH; JoAnn E. Manson, MD, DrPH; Stephen Sidney, MD, MPH;
Maurizio Trevisan, PhD; for the Women's Health Initiative Investigators
Background-Individuals with vascular or valvular calcification are at increased risk for coronary events, but the
relationship between calcium consumption and cardiovascular events is uncertain. We evaluated the tisk of coronary and
cerebrovascular events in the Women's Health Initiative randomized tiial of calcium plus vitamin D supplementation.
Methods and Results-We randomized 36 282 postmenopausal women 50 to 79 years of age at 40 clinical sites to calcium
carbonate 500 mg with vitamin D 200 IU twice daily or to placebo. Cardiovascular disease was a prespecified secondary
efficacy outcome. During 7 years of follow-up, myocardial infarction or coronary heart disease death was confirmed for
499 women assigned to calcium/vitamin D and 475 women assigned to placebo (hazard ratio, 1.04; 95% confidence
interval, 0.92 to 1.18). Stroke was confirmed among 362 women assigned to calcium/vitamin D and 377 assigned to
placebo (hazard ratio, 0.95; 95% confidence interval, 0.82 to 1.10). In subgroup analyses, women with higher total
calcium intake (diet plus supplements) at baseline were not at higher risk for coronary events (P= 0.91 for interaction)
or stroke (P= O. l4 for interaction) if assigned to active calcium/vitamin D.
Conclusiom-Calciumlvitamin D supplementation neither increased nor decreased coronary or cerebrovascular risk in
generally healthy postmenopausal women over a 7-year use period. (Circulation. 2007;115:846-854.)
Key Words: calcium cerebrovascular disorders coronary disease stroke women
V
ascular calcification and valvular calcification predict ath-
erosclerotic risk
1

2
and are prevalent in cluonic diseases
such as diabetes,
3
systemic lupus erythematosus,
4
and chronic
kidney disease,
5
in which the risk of coronary events is high.
Arterial calcification and valvular calcification are organized,
regulated processes similar in many respects to bone fonnation
and remodeling.
6
-9 Because of this relationship, bisphospho-
nates have been proposed as antiatherosclerotic agents,
10
and
patients with coronruy calcification commonly ask if they should
reduce their calcium consumption.
11
The literature on this topic
is scant and contlicting
12
-
16
; even less is known about the
relationship between vitamin D and coronruy risk.
17
Editorial p 827
Clinical Perspective p 854
We randomized 36 282 postmenopausal women to calcium
plus vitamin D or to placebo in a fracture trial and report here
Received November 2, 2006; accepted December 14, 2006.
the impact of 7 years of supplementation on cardiovascular
outcomes, including time trends and analyses of subgroups.
Methods
Details of the study design have been published previously,
18
as have
the baseline characteristics.
1
9-
2 1
Eligible postmenopausal women 50
to 79 years of age joined the Women's Health Initiative hormone
therapy and/or dietary modification trials between 1993 and 1998.
One year later, they were invited to join the double-blinded calcium
plus vitamin D trial; 91 % joined the calcium/vitamin D trial at their
first annual visit and 9% during the following year. Women provided
written informed consent in a fom1 approved by local institutional
review boards and were randomly assigned to calcium carbonate 500
mg with 25-hydroxy vitamin D
3
200 IU twice daily or matching
placebo (GiaxoSmithKiine, Research Triangle P<uk, NC). Concur-
rent calcium supplementation was pennitted, as was vitamin D. up to
400 IU daily.
From the Department of Medicine, George Washington University, Washington, DC (J.H.); Department of Epidemiology, University of North Carolina School
of Public Health, Chapel Hill (G.H.); Fred Hutchinson Cancer Research Center, Seanle, Wash (H.R.); Department of Family and Preventive Medicine. University
of California at San Diego, San Diego (M.A.); Departments of Medicine (N.C.D., P.G.) and Preventive Medicine (P.G.), NOithwestern University, Chicago, Ill;
Depmtment of Epidemiology, University of Washington, Seattle (S.R.H.); Depattment of Preventive Medicine, University of Tennessee Health Science Center,
Memphis (K.C.J.); Division of Preventive Medicine. Brigham and Women's Hospital and Harvard Medical School, Boston, Mass (J.E.M.); Kaiser Penuanente,
Oakland, Calif (S.S.); and University at Buffalo School of Public Health and Health Professions, Buffalo, NY (M.T.).
Clinical trial registration information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
The online-only Data Supplement, consisting of a list of investigators, is available with this article at http://circ.ahajournals.orglcgi/content/full/
ClRCULA TIONAHA.l06.673491/DC1.
Guest Editor for this article was Robert H. Eckel , MD.
Correspondence to Judith Hsia, MD, 2150 Pennsylvania Ave, NW No. 4- 414, Washington, DC 20037. E-mailjhsia@mfa.gwu.edu
2007 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org DOl: 10.1161/CJ.RCULA TIONAHA.106.673491
846
Hsia et al
Clinical Outcomes
Weight, blood pressure, and waist circumference were recorded
annually. Blood samples were collected at baseline, ie, at the time of
enrollment into the hormone therapy and/or dietary modification
trials, from all participants; in a random 6% sample, blood samples
also were collected I and 3 years later.
22
Participants reported emergency room visits, overnight hospital
stays, and outpatient coronary revascularization procedures semian-
nually. Medical records for all overnight hospitalizations and outpa-
tient coronary revascularization procedures were scruti nized for
potential outcomes of interest . Centrally trained physician-
adjudicators classified outcomes on the basis of medical record
review. Myocardial infarction was categorized through the use of an
algorithm that included symptoms, ECG findings, and cardiac
enzymes.23 Confirmed angina required hospitalization for angina
with confirmatory stress test or obstructive coronary disease by
angiography.
14
Stroke required rapid onset of a persistent neurolog-
ical deficit not due to trauma, tumor, infection, or other cause
25
;
strokes were coded as "other" if procedure related or if the adjudi-
catm: could not classify the event as hemorrhagic or ischemic. All
deaths were centrally adjudicated; other outcomes were adjudicated
on the basis of hospital record review by centrally trained, local
adjudicators blinded to treatment assigrunent. Composite outcomes
were defined during development of the analytical plan.
Statistical Methods
Statistical methods have been described.
20

21
In brief, hazard ratios
with 95% confidence intervals (Cls) were calculated from Cox
proportional-hazards models stratified by age, prevalem cardiovas-
cular disease at baseline. and randomization status in the hormone
and dietary modification trials. Subgroup analyses were planned
a priori. Subgroup analyses were stratified by age. prevalent cardio-
vascular disease at baseline, and randomization status in the hormone
and dietary modification trials. Consistency of treatment effects
among subgroups was assessed by formal tests of interaction; tests
for linear trend were used when appropriate. Nineteen subgroups
were evaluated for coronary heart disease (CHD) and for stroke;
subgroup results should be interpreted with caution because 1
significant finding would be expected by chance for each outcome
based on a 0.05 nominal level of statistical significance. All reported
probability values are 2 sided. Analyses were carried out by the
coordinating center statistics unit using the SAS System for Win-
dows, version 9 (SAS Institute. Cary, NC).
The authors had full access to and take responsibility for the
integrity of the data. All authors have read and agree to the
manuscript as written.
Results
Between 1995 and 2000, 36 282 women were randomized at
40 clinical sites; when the trial closed in April 2005, the mean
duration of follow-up was 7 .0:!: L4 years. Baseline character-
istics were balanced between treatment groups (Table I)
except for hypertension (P=0.03). At baseline, mean calcium
intake (diet plus supplements. exclusive of study medication)
was 1148:!:654 mg/d in the active treatment group and
1154:!: 658 mg/d in the placebo group, close to the recom-
mended intake of 1200 mg dai ly.
26
Vitamin D consumption
was 365:!:265 IU/d in the active treatment group and
368:!:266 IU/d in the placebo group. Sixty percent of study
participants took at least 80% of their study medication
through year 6.
Intermediate Biomarkers and Risk Factors for CUD
Although blood samples were collected on the entire cohort,
bioassays were performed in only a 6% random sample. At
baseline, total cholesterol was 5.64 mmoi/L, low-density
lipoprotein cholesterol was 3.28 mmoi/L, high-density li -
Calcium/Vitamin D and Cardiovascular Risk 847
poprotein cholesterol was 1.54 mmoi/L, triglyccrides were
1.81 mmoi!L, glucose was 5.49 mmoi!L, and insulin was II A
~ L l U / m L Differences between mean percent. change in the
intervention group and mean percent change in the control
group are shown from baseline to year 2 after randomization
(Figure 1). Percent change from baseline differed signifi-
cantly between treatment groups for low-density lipoprotein
cholesterol (P=0.02), waist circumference and weight
(P=0.03 for both), systolic blood pressure (P=O.Ol), and
diastolic blood pressure (P<O.OI).
Clinical Cardiovascular Outcomes
Myocardial infarction or CHD death was confirmed in 499
women assigned to active calcium/vitamin D and 475 as-
signed to placebo (hazard ratio, 1.04; 95% CI, 0.92 to 1.18).
Stroke was confirmed in 362 women assigned to calcium/
vitan1in D and 377 assigned to placebo (hazard ratio, 0.95;
95% CI, 0.82 to 1.10; Figure 2). Among women taking at
least 80% of study medication, the hazard ratio for myocar-
dial infarction/CHD death was 1.05 (95% CJ, 0.88 to 1.25)
and for stroke was 0.97 (95% cr. 0.79 to 1.20) (data not
shown). Risks of coronary revascularization, confirmed an-
gina, hospitalized heart failure, transient ischemic attack, and
composite outcomes also were similar in the 2 treatment
groups (Table 2).
Temporal Trends
Hazard ratios with nominal 95% Cis for myocardial infarc-
tion/CHD death at 1-year intervals of follow-up were as
follows: year l, 1.13 (95% CI, 0.79 to 1.61); year 2, 1.10
(95% CI, 0.75 to 1.61); year 3, 1.00 (95% Cl , 0.69 to 1.46);
year 4, 0.92 (95% Cl, 0.66 to 1.28); year 5, 1.00 (95% CI,
0.72 to 1.39), year 6, 1.11 (95% CI, 0.81 to 1.51 ), and year
?.7, 1.07 (95% Cl, 0.80 to 1.42). The z score for trend, based
on Cox proportional-hazards modeling with time-dependent
treatment effects, was 0.22 (P= 0.82), indicating no signifi-
cant trend in tisk over time.
Hazard ratios with 95% Cis for stroke were as follows:
year 1, 1.09 (95% CI, 0.69 to 1.72); year 2, 0.62 (95% CI,
0.41 to 0.94 ); year 3, 1.22 (95% Cl, 0.82 to I .82); year 4, 1.07
(95% CI, 0.70 to 1.65); year 5, 1.01 (95% Cl, 0.69 to 1.47),
year 6, 0.71(95% CI, 0.50 to 1.01), and year ?.7, 1.11 (95%
cr. 0.81 to 1.52). The z score was 0.55 (P=0.58).
Trends by Age
Cumulative hazard ratios for myocardial infarction/CHD
death and for stroke were evaluated by age decade. For
women 50 to 59, 60 to 69, and 70 to 79 years of age at
baseline, hazard ratios with 95% Cis for CHD were 0.94
(95% Cl, 0.70 to 1.27), 1.08 (95% C1, 0.90 to 1.30), and 1.05
(95% CI, 0.85 to 1.30), respectively (P= 0.53 for interaction).
Hazard ratios with 95% Cis for stroke were 0.90 (95% CI,
0.62 to 1.32), 0.97 (95% Cl, 0.78 to 1.20), and 0.96 (95% Cl,
0.76 to 1.20), respectively (P=0.72 for interaction).
Additional Subgroup Analyses
We evaluated several demographic and clinical characteristics to
determine whether other subgroups of women were at lower or
higher risk for myocardial infarction/CHD death with calcium!
848 Circulation February 20, 2007
TABLE 1. Baseline Characteristics by Treatment Group Assignment
CalciumNitamin D Placebo
(N=18 176) (N=18106)
p
Age, y 62.4:!: 7.0 62.4:!:6.9 0.97
Body mass index, kg/m
2
29.1 :!: 5.9 29.0 5.9 0.24
Waist circumference, em 88.9:!:13.7 88.8 13.7 0.46
Systolic blood pressure, mm Hg 12717 128 17 0.48
Diastolic blood pressure, mm Hg 76:!:9 76:!:9 0.56
Total calcium intake (supplements, diet, and medications), mg/d 1148654 1154658 0.40
Total vitamin D intake (supplements and diet), IU/d 365 265 368 266 0.36
Vitamin D intake (supplements), IU/d 190235 192235 0.46
Vitamin D intake (diet), IU/d 175117 176117 0.47
Elhnicity 0.45
White 15 047 (82.8) 15 106 (83.4)
Black 1682 (9.3) 1635 (9.0)
Hispanic 789 (4.3) 718 (4.0)
American Indian/Alaskan native 77 (0.4) 72 (0.4)
Asian/Pacific islander 369 (2.0) 353 (1.9)
Unknown 212(1.2) 222 (1.2)
Hypertension 0.03
None 10 915 (66.7) 10 858 (66.5)
Untreated 1260 (7.7) 1384 (8.5)
Treated 4187 (25.6) 4092 (25.1)
Diabetes mellitus 1055 (5.8) 1036 (5.7) 080
High cholesterol requiring pills 2008 (12.3) 1964 (12.1) 0.49
Cigarette smoking 0.31
Current 1405 (7.8) 1356 (7.6)
Past 7255 (40.3) 7133 (39.8)
Never 9325 (51.8) 9428 (52.6)
CHD at baseline 487 (2.7) 456 (2.5) 0.34
Cardiovascular disease at baseline 881 (4.8) 860 (4.7) 0.66
Stalin use 1178 (6.5) 1149 (6.3) 0.60
Aspirin use 3552 (19.5) 3517 (19.4) 0.78
NSAID use 5983 (32.9) 5891 (32.5) 0.44
Use of postmenopausal hormone therapy
Assigned to active therapy in hormone trials 4039 (22.2) 4078 (22.5) 0.49
Current use, including exposure in hormone trials 9358 (51 .5) 9484 (52.4) 0.09
NSAID indicates nonsteroidal antiinflammatory drug, including aspirin; CHD at baseline, self-reported myocardial
infarction or coronary revascularization at baseline; cardiovascular disease at baseline, self-reported myocardial infarction,
coronary revascularization, stroke, or transient cerebral ischemia at baseline; aspirin use, >80 mg taken at least twice
weekly; and stalin, 3' -hydroxy-3-methyglutaryl coenzyme A reductase inhibitor. Values are meanSD or n (%).
vitamin D (Figure 3) or for stroke (Figure 4). The hazard ratios
for CHD (P=0.91 for interaction) and stroke (P=O.J4 for
interaction) did not differ by total calcium intake (dietary plus
supplemental) at baseline. Similarly, hazard ratios did not differ
by vitamin D intake at baseline (P=0.45 for interaction for CHD
and P =O.l2 for stroke). Hazard ratios also did not differ by
ethnicity, although numbers of events were small among His-
panic, American Indian, and Asian women (P=0.54 for inter-
action for CHD and P=0.63 for stroke).
CHD risk with active calcium/vitamin D was inversely related
to body mass index (P =0.04 for interaction); ie, women with
higher body mass index were at lower CHD 1isk with active
calcium/vitamin D supplementation, whereas those with lower
body mass index were at higher CHD risk. Stroke risk with
active calcium/vitamin D was lower among women with high
cholesterol and those taking statins at baseline (P=0.04 for
interaction for both). Stroke risk with active calcium/vitamin D
was inversely related to the number of CHD risk factors; ie,
women with fewer risk factors were at higher stroke risk with
calcium/vitamin D supplementation (?=0.02 for interaction).
Discussion
Calcium/vitamin D supplementation neither increased nor
decreased the risk for CI-ID or stroke in generally healthy
Hsia et al Calcium/Vitamin D and Cardiovascular Risk 849
Total Cholesterol
Triglyceride
HDLC
LDLC
Insulin
Glucose
HOMA
WHR
Waist
Weight
Systolic BP
Diastolic BP
-20
-6.1
-6.7
-15 -10
~
-0.9 ~
: ~
t.4
_.( 0.4
-5 0 5
Figure 1. Differences in mean percent
change from baseline to year 2 between
women assigned to active calcium/vita-
min D and those assigned to placebo for
several intermediate outcomes. Horizon-
tal lines represent 95% Cis. Physical
measures were performed on the entire
cohort; laboratory measures, in a random
6% subsample. Treatment group differ-
ences were significant for low-density
lipoprotein cholesterol (LDL-C; P= 0.02),
waist circumference and weight {both
P=0.03), and systolic (P=0.01) and dia-
stolic (P< 0.01) blood pressures. HDL-C
indicates high-density lipoprotein choles-
terol; HOMA, homeostasis model
assessment; WHR, waist-to-hip ratio;
and BP, blood pressure.
Mean Percent Change lrom Baseline in the Intervention Group
postmenopausal women throughout the 7-year duration of
this randomized trial. Neither total calcium intake (dietary
plus supplemental) nor total vitamin D intake at baseline
affected cardiovascular risk with calcium/vitamin D
supplementation.
Possible explanations of this null finding include the
following: ( 1) Background calcium use impaired our ability
to identify a treatment effect; (2) the dose of vitamin D was
inadequate; (3) poor adherence to study medication blunted
any treatment effect: (4) concurrent postmenopausal hormone
therapy interfered with treatment effects; (5) the trial was
designed to evaluate the effects of calcium/vitamin D supple-
mentation on fracture, not cardiovascular disease; or (6)
calcium and vitamin D do not, in fact, affect cardiovascul ar
risk.
0.06
0.06
0.04
I
I
0.03
0.02
0,01
0.00
:.:::.
HR 1.04
95l(.CI 10.92,1.18)
0 .. ..
0 .. ..
,.,,
-
,,..
*'"'
.,.,.,
-
..
3
.. ..
,.
..
"
,.
""'
,,... ,,..
, ....
" ..
-
----
IUI!ber"de.oetlts
....,_,.""'
--- -..
--Cored
. ~
/.?
.-
"
~ ~
_....,;
6
.. .. ..
77 ..
"
- - -
- - -
A limitation of the trial was that women were allowed to
continue their own calcium supplements because it would
have been unethical to prohibit concunent calcium use in a
long-term, placebo-controlled trial. Baseline calcium con-
sumption (diet plus supplements) was balanced between
treatment groups, and no significant interaction between
dietary or total calcium consumption at baseline and random-
ized treatment assignment was observed for either CHD or
stroke.
Baseline vitamin D consumption (diet plus supplements)
and regional solar irradiance
21
also were balanced between
treatment groups. Parathyroid hormone levels are maximally
suppressed at 25-hydroxy vitamin D blood levels > 75
nmol/L (30 ng/mL).
27
In our trial , despite consuming 365 IU
vitamin D daily (supplements plus dietary vitamin D) at
--- -..
--Control
Q.04
i
"
t
J
Q03
OD2
.
,.
.. ..
.,
..
"'
..
"'
-
. .. 57 .. .. .. 72 ..
,.
..,.
...
"""
,,.. ,,...
-
"""
-
..,.
..... ..... ......
""" '""
,,.,
.....
""
-
----
_ ........
N:lmln ... Airl<
Figure 2. Kaplan-Meier estimates of cumulative hazard rates for CHD (myocardial infarction or coronary death; left) and for stroke
(right). HR indicates hazard ratio.
850 Circulation February 20, 2007
TABLE 2. Cardiovascular Events by Treatment Group Assignment
CalciumNitamin 0 Placebo
(N=18176), (N=18106), Hazard Ratio
n (Annualized %) n (Annualized %) (95% Cl)
p
Myocardial infarction or CHD death 499 (0.39) 475 (0.37) 1.04 (0.92-1.18) 0.50
Myocardial infarction 411 (0.32) 390 (0.31) 1.05 (0.91-1.20) 0.52
CHD death 130 (0.10) 128(0.10) 1.01 (0.7!H.29) 0.92
CABG or PCI 674 (0.53) 607 (0.48) 1.09 (0.98-1.22) 0.12
Myocardial infarction/CHD death/CABG/PCI 920 (0.72) 841 (0.66) 1.08 (0.99--1.19) 0. 10
Confirmed angina 404 (0.32) 377 (0.30) 1.08 (0.94-1.24) 0.30
Hospitalized heart failure 394 (0.31) 407 (0.32) 0.95 (0.83-1.10) 0.50
Stroke 362 (0.28) 377 (0.30) 0.95 (0.82- 1.10) 0.51
lschem ic stroke 225 (0.18) 228 (0.18) 0.98 (0.82-1.18) 0.84
Hemorrhagic stroke 58 (0.05) 68 (0.05) 0.84 (0.59--1.19) 0.33
Other stroke 63 (0.05) 57 (0.04) 1.11 (0.77-1.59) 0.58
Transient ischemic attack 213 (0.17) 182 (0.14) 1.16 (0.95-1.42) 0.13
Stroke/transient ischemic attack 563 (0.44) 547 (0.43) 1.02 (0.91-1.15) 0.75
CABG indicates coronary artery bypass grafting; PCI, percutaneous coronary intervention. Numbers of events do not
add up to the totals for categories because some women had > 1 event.
baseline, only 13% of women with incident fractures
(n= 1589) and 15% of matched controls had serum levels
>75 nmol!L, consistent with the current view that 800 to
I 000 JU daily may be needed to achieve optimal serum
vitamin D levels.
2
R Women assigned to active calcium!
vitamin D supplementation would have been taking almost
800 IU daily, which may still have been insufficient. None-
theless, women with higher vitamin D consumption at base-
line were not at higher or lower risk for CHD or stroke if
assigned to active calcium/vitamin D. Low vitamin D levels
have been associated with acute stroke
29
; because we mea-
sured serum vitamin D levels in fracture cases and controls,
not stroke cases, we are not able to confirm this association.
At the end of the trial (mean follow-up, 7 years), 76% of
participants were taking some study pills, and 59% were
taking 2:80% of their study medication. Calcium/vitamin D
supplementation did not alter CHD or stroke risk in sensitiv-
ity analyses, in which women were censored when they
became nonadherent, reducing the likelihood that adherence
affected study results. Use of postmenopausal hormone ther-
apy, which increases the risk of stroke
2
5 and CHD,30 was
balanced in the treatment groups. Neither CHD nor stroke
risk differed with calcium/vitamin D supplementation among
women assigned to active hormone therapy in the randomized
hormone trials, making it unlikely that postmenopausal hor-
mone use affected study results.
Another limitation of our analysis is that this trial was
designed to evaluate the effect of intervention on fracture, not
cardiovascular disease. Jn fact, the number of myocardial
infarctions/CHD deaths (n=974) and strokes (n=739) was
greater than the number of hip fractures (n=374), so a
reasonable treatment effect should have been readily detect-
able. Overall, the most likely explanation for our findings is
that calciumlvitamin D supplementation did not modulate
CHD or stroke risk.
Calcium and vitamin D had a mixture of favorable and
unfavorable effects on intermediate outcomes. Systolic pres-
sw-e rose l.l :t 12.4% among calcium/vitamin D recipients
during the 2 years after randomization and 0.7:!: 12.4%
among placebo recipients (P=O.OI for the treatment group
difference in percent change from baseline to year 2).
Diastolic pressure fell 0.2:!: 12.4% in the active treatment
group and 0.6:!: 12.4% in the placebo group (?=0.007).
These findings contrast with the National Health and Nutri -
tion Examination Survey, in which dietary calcium consump-
tion was inversely associated with an age-related increase in
systolic blood pressure.
3 1
Because of adjustments in concur-
rent medication dosage, we cannot be sure that the treatment
group differences in our trial are due solely to calcium/
vitamin D supplementation. Furthermore, in later years of the
trial, the changes in blood pressure from baseline no longer
differed between treatment groups.
Weight increased in both treatment groups during the 2
years after randomization (1.4:!: 10.5% versus 1.7:!: 12.0%),
as did waist circumference (1.5:!:7.6% versus 1.8:!:8.4%), but
these increases were smaller among women assigned to
active calciumlvitamin D (?=0.03 for both). The relationship
between weight and calcium/vitamin D consumption in other
reports has been inconsistent ,
32

33
but women taking calcium
supplements gained less weight than nonusers in a recent,
large, 10-year epidemiological study. 3
4
In both treatment groups, low-density lipoprotein choles-
terol rose in the 6% of participants with measured biomark-
ers, but the increase was smaller among women assigned to
active calcium/vitamin D (0.2:!:20.9% versus 2.6:!:20.7%;
? =0.02). Tn a small 12-week trial, calcium/vitamin D sup-
plementation had no effect on low-density lipoprotein cho-
lesteroP5 The modest difference seen in our trial may reflect
changes in weight over the 2 years or adjustments in
concomitant medications and cannot be definitively attributed
to calciumlvitamin D supplementation.
We found several subgroups of women with lower hazard
ratios for CI-ID or stroke with calcium/vitamin D supplemen-
tation. Women with higher body mass index appeared to be at
Hsia et al
P Vatuefor
Subgroup CaD Placebo Interaction
No. ol cases or CHD
(annuaized percentage)
0.0
Age ' yrs
50-59 84 (0.17)
87 (0.18) ]
6069 239 (0.42) 220 (0.39) 0.53
7().79 t76 (0.82) 168 (0.79)
Body mass index, kglm
2
<25 107 (0.32)
95 (0.28) ]
25 - <30 186 (0.41) 158 (0.35) 0.04
~ 3 0
205 (0.43) 220 (0.47)
Waist circumference, em
<85 t57 (0.29)
135 (0.25) ]
85 - <97 170 (0.43) 160 (0.41) 0.11
~ 9 7 172 (0.51) 178 (0.53)
Diabetes
No diabetes 409 (0.34)
394 (0.33) ]
0.84
All diabetes 89 (1.24) 81 (1.17)
Smoking
Yes 60 (0.62) 54 (0.57) ]
0.81
No 432 (0.37) 413 (0.35)
Hypertension
Yes 279 (0.59)
289 (0.61) ]
0.16
No 180 (0.26) 150 (0.22)
High cholesterol requiring pins
Yes 111 (0.83)
108 (0.83) ]
0.74
No 321 (0.33) 307 (0.31)
CHD risk factors
None 106 (0.19)
88 (0.16) ]
12 298 (0.55) 292 (0.55) 0.14
<:3
18 (1.33) 26 {1.86)
CHD at baseline
Yes 66 (2.05)
67 (2.23) ]
0.52
No 433 (0.35) 408 (0.33)
CVD at baseline
Yes 90 (1.53)
85 (1.49) ]
0.87
No 409 (0.33) 390 (0.32)
Slatin use al baseline
Yes 72 (0.91) 66 (0.87) ]
0.95
No 427 (0.35) 409 (0.34)
Aspirin use (<: 80 mQiday) at baseline
Yes 145 {0.59)
129 (0.53) ]
0.48
No 354 (0.34) 346 (0.34)
Dietary calcium Intake, mg
<800 300 (0.43)
286 (0.41) ]
800- <1200 108 (0.32) 115 (0.34) 0.52
2: 1200 73 (0.34) 63 (0.29)
Total calolum Intake, mg
<800 210 (0.49)
181 (0.43) ]
800 -<1200 128 (0.38) 125 (0.38) 0.91
2: 1200
143 (0.29) 158 (0.32)
To1alvitamin 0 intake, IU
<200 195 (0.40)
"' ... , l
200 <400 78 (0.33) 89 (0.37)
0.45
400 <600 119 (0.41) 103 (0.34)
~ 6 0 0 89 (0.38) 80 (0.35)
Alcohol use
Non d drink per week 354 (0.44)
332 (0.42) J
1 - < 7 drinks per week 92 (0.28) 95 (0.28) 0.84
7 + drinks per week 43 (0.32) 42 (0.32)
HRT arm
No1enrolled 241 (0.33)
238 (0.33) ]
ActiVe 129 (0.46) 116 (0.41) 0.69
Placebo 129 (0.46) 121 (0.44)
OM arm
Not enrolled 180 (0.47)
163 (0.43) ]
Intervention 131 (0.39) 128 (0.37) 0.65
Comparison 188 (0.34) 184 (0.34)
Calcium/Vitamin D and Cardiovascular Risk
Hazard Ratio
0.5
(-- 95% Ct - --l
1.0 1.5
.
0.94 '
!
1.08
'
1.05
.
.
'
1.16
.
0.91 '
1.18
'
'
'
'
1.17
i
1.02
0.96
'
.
.
.
1.04
1.05
'
'
1.04
1.04
'
I
0.98
I
' 1.17
.
.
0.98
.
'
1.04
I
I
'
1.19
.
1.01
0.68
I
I
I
0.89 '
1.06
I
I
I
1.04
1.04
'
~ 0 0
1.04
I
' .
1.13
.
'
1.02
I
I
1
1.03
0.93
I
' 1.21
' I
I
1.12
'
0.93
.
1.01
' I
0.97
I
I
0.91
I
I
1.19
'
1.07

I
I
.
1.05
0.95
I
1.07
.
I
0.99
I
I
I
1.13
;
I
1.08
I
I
1.1 1
' 1.05
0.97
.
851
2.0
Figure 3. Risk of CHD (myocardial infarction or CHD death) by treatment group assignment in various subgroups. Hazard ratios with nominal 95%
Cis {horizontal bars) are adjusted for age and prevalent CHD at baseline. The red dotted vertical line represents the hazard ratio for CHD in the over-
all cohort. Probability values are for the interaction between the subgroup variable and treatment assignment. CHD includes nonfatal myocardial
infarction and coronary death. Hypertension was defined as treated hypertension or a measured blood pressure of 2:140190 mm Hg. Risk factors
for CHD included current cigarette smoking, hypertension, self-reported diabetes, and high cholesterol. The presence of CHD at baseline was
defined as self-reported myocardial infarction or coronary revascularization. The presence of cardiovascular disease (CVD) at baseline was defined
as self-reported myocardial infarction, coronary revascularization, stroke, or transient cerebral ischemia. Because of missing data on some variables,
the numbers of cases do not always add up to the total number of cases in the treatment group. Statin indicates 3'-hydroxy-3-methylglutaryl coen-
zyme A reductase inhibitor, HRT, hormone replacement trial; OM, dietary modification trial; and CaD, calcium plus vitamin D.
852 Circulation February 20, 2007
Subgroup cao Placebo
No. ol cases of Stroke
(annualized percentage)
Age, yrs
5(}-59 51 (0.10)
56 (0.11) J
6(}-69 164 (029) 170 (0.30)
7(}-79 147 (0.69) 151 (0.71)
Body mass index, kg/m
2
<25 96 (028)
95 (028) ]
25- <30 129 (028) 140 (0.31)
;,.30 136 (028) 142 (0.30)
Waist circumference, em
<85 130 (0.24)
142 (0.26) ]
85. <97 l17 (029) 130 (0.33)
~ 9 7 115 (0.34) 102 (0.30)
Diabetes
No diabetes 318 (0.26) 324 (027) J
All diabetes 44 (0.61) 53 (0.77)
Smoking
Yes 36 (0.37)
33 (0.35) ]
No 322 (0.27) 339 (029)
Hypertenslon
Yes 215 (0.45)
242 (0.51) ]
No 124 (0,18) 103 (0.15)
High cholesterol requiring pins
Yes 45 (0.33) 65 (0.50) ]
No 273 (028) 262 (0.27)
CHD risk factOfs
None 85 (0.15)
75 (0.14) ]
1-2 220 (0.41) 238 (0.45)
"3
7 (0.52) 8 (0.57)
CHD at baseline
Yes 19 (0.59)
30 (1.00) ]
No 343 (0.27) 347 (028)
CVD at baseline
Yes 41 (0.70) 58 (1.01) ]
No 321 (0.26) 319 (0.26)
Statin use at baseHne
Yes 21 (0.27)
36 (0.47) ]
No 341 (028) 341 (028)
Aspirin use ("' 80 mg/day) at baseHne
Yes 99 (0.40) Ill (0.46) ]
No 263 (0.25) 266 (0.26)
Dietary calcium intake, mg
<800 202 (029)
205 (029) ]
800. <1 200 93 (0.27) 91 (0.27)
~ 1200 57 (027) 70 (0.32)
Total calcium Intake. mg
<800 139 (0.32)
127 (0.30) ]
800- <1 200 92 (028) 87 (0.27)
" 1200
121 (0.25) 152 (0.31)
Total vitamin o intake. IU
<200 139 (028)
130 (0.27) l
200 - <400 76 (0.32) 76 (0.31)
400 - <600 82 (028) 86 (029)
"600
55 {0.23) 74 (0.32)
Alcohol use
Non - <I drink per week 243 (0.30)
253 (0.32) J
I - < 7 drinks per week 76 (0.23) 84 (0.25)
7 +drinks per week 39 (029) 37 (028)
HRTarm
Not enrolled 182 (0.25)
194 (0.27) ]
Active 97 (0.34) 110 (0.39)
Placebo 83 {0.30) 73 (027)
DMarm
Not enrolled 126 (0.33)
120 (0.32) J
Intervention 90 (0.26) 94 (027)
Comparison 146 (0.26) 163 (0.30)
P Value tor
Interaction
0.72
0.98
0.60
0.26
0.64
0.06
004
0.02
0.08
0.11
0.04
0.51
0.58
0.14
0.12
085
0.44
0.44
0.0
(-95%CI-) Hazard Ratio
0.5 1.0 1.5
0.90
0.97
.
0.96
0.92
1.04
0.93
0.92
0.86
1.12
0 9 8 ~
-
0.78
:
0.95---+
1.01
-
0.88
1.19
0.69
'
t
1.04
1.14
0.90
~
0.76
' .
'
0.61
0.99-t -
0.71
0.99:'
,....._
0.54
!
--l.
.---1.00
.
0.89
0.99
:
0.97
0.98
~
0.85
~
1.07
. .04
0.80
l 1.02
0.98
:
1.04
0.74
0.96
0.90
0.92
0.90
1.14
0.99
1.05
0.86
2.0 2.5
1.12
Fi gure 4. Risk of stroke by treatment group assignment in various subgroups. Hazard ratios with nominal 95% Cis (horizontal bars) are
adjusted for age and prevalent cerebrovascular disease at baseline. Abbreviations as in Figure 3.
lower risk for CHD with calcium/vitamin D supplementation
(?=0.04 for interaction), but in view of the number of
subgroups examined, this finding may be due to chance.
We also found that women with more coronary risk factors
were at lower risk for stroke with calcium/vitamin D supple-
mentation (?=0.02 for interaction) but think this may be due
to chance as well, particularly because the number of women
with ;;:::3 risk factors was very small. On the other hand,
women with self-reported hypercholesterolemia and those
who used statins were at lower risk for stroke if assigned to
active calcium/vitamin D (?= 0.04 for interaction for both).
The clinical link between high cholesterol and stalin use and
the proposed, albeit controversial, effect of stalin use on bone
enhance the plausibility of this interaction.
Statins increase new bone fonnation in vitro and enhance
trabecular bone formation in rodents
36
through blockade of
Hsia et al
the mevalonate pathway.
37
In women, as opposed to rodents,
statins had no effect on markers of bone turnover,
38
bone
density, fracture risk,39 or progression of coronary calcifica-
tion40; thus, the relationship between statin use and fracture
risk remains controversial. Overall , the relationship between
consumption of calcium/vitamin D supplements and statin
use remains quite unclear with regard to cardiovascular
disease risk. Another placebo-controlled trial the size and
duration of the Women's Health Initiative is unlikely to be
undertaken, although it is possible that trials of bisphospho-
nates or other agents may shed some light. Populations in
those trials are not at particularly high risk for cardiovascular
disease, however, so the number of atherosclerotic events
may prove inadequate.
Calcium and vitamin D supplementation did not increase
the risk for myocardial infarction, CHD death, stroke, coro-
nary revascularization, hospitalized angina, heart failtue, or
transient ischemic attack. Thus. women taking these supple-
ments need not fear adverse cardiovascular consequences
while protecting their bone health.
Source of Funding
The Women's Health Initiative program is funded by the National
Heart, Lung, and Blood Institute, United States Department of
Heallh and Human Services.
Disclosures
Dr Hsia received a research g rant from GlaxoSmithKline. The other
authors report no conflicts.
References
I. Pletcher MJ. Tice JA. Pignone M. Using the coronary artery calcium
score to predict coronary heart disease events: a systematic review and
meta-analysis. Arch Intern Med. 2004; I 64: 1285-1292.
2. Allison MA, Cheung P, Criqui MH, Langer Rd, Wright CM . .Mitral and
aortic annular calcification are highly associated with systemic calcified
atherosclerosis. Circulation. 2006; 113:861-866.
3. Reaven PD, Sacks J, for the Investigators for the V ADT. Coronary artery
and abdominal aortic calcification are associated wi th cardiovascular
disease iu type 2 di abetes. Diabetologia. 2005:48:379- 385.
4. Molad Y. Levin-Iaina N, Yaturi M, Sulkes J, Sagie A. Heart valve
calcification in young patients with systemic lupus erythematosus: a
window to premature atherosclerotic vascular morbidity and a risk factor
for all-cause mortality. Atlwrosclerosis. 2006; 185:406-4 I 2.
5. Jono S. Shioi A. Ikari Y. Nishizawa Y. Vascular calcificat ion in chronic
kidney disease . ./ Bone Miner Metab. 2006;24:176-181.
6. Anand DV, Lahiri A, Lim E. Hopkins D, Corder R. The relationship
between plasma osteoprotegerin levels and coronary artery calcification
in uncomplicated type 2 diabetic subjects. J Am Coli Cardiol. 2006:47:
1850-1857.
7. Doherty T.M, Asotra K. Fitapatrick LA, Qiao JH, Wilkin OJ, Detrano RC,
Dunstan CR. Shah PK, Rajavashisth TB. Calcification in atherosclerosis:
bone biology and chronic inflammation at the arterial crossroads. Proc
Nat/ Acad Sci US A. 2003: 100: 11201- 11206.
8. Yattikuti R. Towler DA. Osteogenic regulation of vascular calcification:
an early perspective. Am J Pil ysiol E11docrinol Metab. 2004;286:
E686-E696.
9. Caira FC, Stock SR, Gleason TG, .McGee EC, Huang J, Bonow RO.
Spelsberg TC, McCarthy PM, Rahimtoola SH, Rajamannan NM. Human
degenerative valve disease is associated with up-regulation of low-density
lipoprotein receptor-related protein 5 receptor-mediated bone fom1ation.
./Am Coli Cardiol. 2006:47: 1707-1712
10. Bevilacqua M. Dominguez U, Rosini S. Barbagallo M. Bispbosphonates
and atherosclerosis: why? Lupus. 2005:14:773- 779.
I I. Davis W. Ask the doctor: calcium intake and vascular calcification. Life
Extension Magazine. August 2005. Available at: www.lef.org/magazinc/
mag2005/aug2005_atd_O l.htm. Accessed May 28, 2006.
Calcium/Vitamin D and Cardiovascular Risk 853
12. Umesawa M, lso H, Date C, Yamamoto A, Toyoshima H, Watanabe Y.
Kikuchi S. Koizumi A, Kondo T, lnaba Y, Tanabe N, Tamakoshi A.
Dietary intake of calcium in relation to mortality from cardiovascular
disease. Stroke. 2006;37:20-26.
13. Van der Vijver LP. van der Waal .MA. Weterings KG. Dekker JM,
Schouten EG. Kok FJ. Calcium intake and 28-ycar cardiovascular and
coronary heart disease mortality in Dutch civil servants. /111 J Epitlemiol.
1992;21: 36-39.
14. Bostick RM. Kushi LH, Wu Y. Meyer KA, Sellers TA, Folsom AR.
Relation of calcium. vitamin D, and diary food intake to ischemic heart
disease mortality among postmenopausal women. Am J Epidemiol. 1999:
149:151- 161.
15. Nerbrand C. Svardsudd K, Ek J. Tibblin G. Cardiovascular mortality and
morbidity in seven counties in Sweden in relation to water hardness and
geological settings: the project: myocardial infarction in mid-Sweden.
Eur Heart J. 1992; 13:721-727.
16. Rosenlund M, Berglind N, Hallqvist J. Bellander T, Bluhm G. Daily
intake of magnesium and calcium from drinking water in relation to
myocardial infarction. Epidemiology. 2005;16:570- 576.
17. Kununerow FA. Nutrition imbalance and angiotoxins as dietary risk
factors in coronary heart disease. Am J Clin Nutr. 1979:32:58-83.
18. Women's Health Initiative Study Group. Design of the Women's Health
Initiative clinical trial and observational stttdy. Control Clin Trials. 1998;
19:61-109.
19. Jackson RD. LaCroix AZ, Cauley JA. McGowan J. The Women's Health
Initiative calcium-vitamin D trial: overview and basel ine characteristics
of participants. Ann Epidemiol. 2003;13:S98-Sl06.
20. Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL,
O'Sullivan MJ. Margolis KL. Ockene JK. Phill ips L, Pottem L. Prentice
RL, Robbins J, Rohan TE, Sarto GE, Shanna S, Stefanick ML, Van Hom
L, Wallace RB, Whitlock E, Bassford T, Beresford SA, Black HR. Bonds
DE. Brzyski RG, Caan B, Chlebowski RT, Cochrane B, Garland C. Gass
.M. Hays J. Heiss G. Hendrix SL, Howard BY, Hsia J. Hubbell FA.
Jackson RD, Johnson KC, Judd H. Kooperbcrg CL, Kuller LH. LaCroix
AZ, Lane OS, Langer RD. Lasser NL, Lewis CE. Limacher MC. Manson
JE, for the Women's Health Initiative Investigators. Calcium plus vitamin
D supplementation and the risk of colorectal cancer. N Eng/ J Med.
2006;354:684-696.
21. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE,
Bassford T, Beresford SA, Black HR. Blanchette P, Bond.< DE, Brunner
RL, Brzyski RG. Caan B, Cauley JA. Chlebowski RT. Cununings SR,
Granek I. Hays J . Heiss G. Hendrix SL. Howard BY. Hsia J. Hubbell FA.
Johnson KC. Judd H, Kotchen JM, Kuller LH. Langer RD. Lasser NL,
Limacher MC, Ludlam S, Manson JE, .Margolis KL, .McGowan J, Ockene
JK, O' Sullivan .MJ, Phill ips L, Prentice RL, Satto GE, Stefanick .ML, Van
Hom L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR,
Barad D. for the Women's Health Initiative Investigators. Calcium plus
vitamin D supplemeutation and the risk of fractures. N Errgl J Med.
2006;354:669- 683.
22. Anderson GL, .Manson JE, Wallace R, Lund B, Hall D. Davis S.
Shumaker S, Wang CY, Stein E, Prentice RL. Implementation of the
Women's Health Initiative study design. Ann Epidemiol. 2003:13:
S5-SJ7.
23. Curb JD, McTiernan A, Heckbert SR. Kooperberg C, Stanford J, Nevitt
M. Johnson KC. Proulx-Burns L. Pa<tore L, Criqui M. Daugherty S, for
the WHI Morbidity and .Mortality Committee. Outcomes ascertainment
and adjudication methods in the Women's Health Initiative. Ann Epi-
demiol. 2003; 13:SI22-SI28.
24. Hsia J, Aragaki A, Bloch M, LaCroix AZ, Wallace R. Predictors of
angina vs myocardial infarction from the Women's Health Initiative.
Am J Cardio/. 2004;93:673-678.
25. Wassertheii-Smoller W, Hendrix SL, Limacher M. Heiss G. Kooperberg
C, Baird A. Kotchen T, Curb JD, Black H, Rossouw JE. Aragaki A,
Safford M, Stein E. Laowattana S, Mysiw WJ, for tbe WHI Investigators.
Effect of estrogen plus progestin on stroke in postmenopausal women: the
Women's Health Initiative: a randomi zed trial. JAMA. 2003;289:
2673-2584.
26. Office of Dietary Supplements, National Institutes of Health. Dietary
supplement fact sheet: calcium. Available at: http://dietary-supplemen-
ts.info.nih.gov/factsheets/calcium.asp. Accessed June I. 2006.
27. Vieth R. What is the optimal vitamin D status for health? Prog Biophys
Mol Bioi. 2006:92:26- 32.
28. Reginster JY. Zcgels B, Lejeune E. Micheletti MC, Kvsaz A, Seidel L.
Sarlet N. Influence of daily regimen calcium and vitamin D supplemen-
854 Circulation February 20, 2007
tation on parathyroid hormone secretion. Calcif Tissue 1111. 2002;70:
78- 82.
29. Poole KES, Loveridge N. Barker PJ, Halsall DJ, Rose C, Reeve J.
Warburton EA. Reduced vitamin D in acute stroke. Stroke. 2006;37:
243-245.
30. Manson JE. Hsia J, Johnson KC. Rossouw JE. Assaf AR, Lasser NL.
Trevisan M. Black HR. Heckbert SR. Detrano R. Strickland OL, Wong
ND, Crouse JR, Stein E, Cushman M, for the Women's Health Initiative
Investigators. Estrogen plus progestin and risk of coronary heart disease.
N Eng/ J Med. 2003:349:523- 534.
31. Haijar IM. Grim CE, Kotchen TA. Dietary calci um lowers the age-related
rise in blood pressure in the United States: the NHANES ffi survey . .I C/in
Hypertens. 2003;5: 122-126.
32. Shapscs SA. Hcshka S. Heymsfield SB. Effect of calcium supplemen-
tation on weight and fat loss in women. J Clin Endocriuol Metab.
2004:89:632-637.
33. Barr SI. Increased dairy product or calcium intake: is body weight or
composition affected in humans? J Nutr. 2003: 133:245S- 248S.
34. Gonzalez AJ. White E. Krista! A, Littman AJ. Calcium intake and 10-year
weight change in middle-aged adults . .I Am Diet Assoc. 2006; 106:
1066-1073.
35. Gannagc-Yared MH. Azoury M. Mansour I, Baddoura R, Halaby G,
Naaman R. Effects of a short-term calcium and vitamin D treatment on
serum cytoki nes. bone markers. insulin and li pid concentrations in
heallhy postmenopausal women. J E1ulocrinol Invest. 2003;26:748- 753.
36 . .Mundy G, Garrett R. Harris S. Chan J. Chen D. Rossini G. Boyce B, Zhao
M. Gutierrez G. Stimulation of bone formation in vitro and in rodents by
HMG CoA reductase inhibitors. Science. 1999;286:1946-1949.
37. Fisher JE. Rogers MJ. Halasy JM. Luckman SP, Hughes DE, Masarachia
PJ. Wesolowski G, Russell RG. Rodan GA. Reszka AA. Alendronate
mechanism of action: geranylgeraniol , an intermediate in the mevalonate
pathway, prevents inhibition of osteoclast formation, bone resorption, and
kinase activation in vitro. Proc Nat! Acad Sci US A. 1999:96:133- 138.
38. Hsia J. Morse M. Levin G. Effect of sinwastatin on bone markers in
osteopenic women: a placebo-controlled, dose-ranging uial. BMC Mus
culoskeletal Disorders. 2002:3:7.
39. LaCroix AZ. Cauley JA. Peltingcr M. Hsia J. Bauer DC, McGowan J.
Chen Z, Lewis CE. McNeeley SG, Passaro MD. Jackson RD. Statin use,
clinical fracture, and bone density in postmenopausal women: results
from the Women's Health Initiative Observational Study. Ann lntem
Med. 2003;139:97- 104.
40. Raggi P, Davidson M. Callister TQ, Welty FK. BacbmaruJ GA, Hecht H,
Rumberger JA. Aggressive versus moderate lipid-lowering therapy in
hypercholesterolemic postmenopausal women: Beyond Endorsed Lipid
Lowering With EBT Scannjng (BELLES). Circulation. 2005; 112:
563- 571.
CLINICAL PERSPECTIVE
Use of calcium and vitamin D supplements is widespread, particularly among older women. In observational studies,
calcium has been associated wilh lower blood pressure and weight loss, which might be expected to lower Jisk for coronary
heart disease and stroke. On the other hand, individuals with coronary artery calcification are at higher tisk for coronary
events, raising concern among patients Lhat calcium supplementation may be deleterious. In the Women's Health Initiative
placebo-controlled trial, calcium 1000 mg plus vitamin D 400 IU daily neither increased nor decreased the risk of coronary
heart disease or stroke during a 7 -year follow up of 36 282 postmenopausal women. Thus, women taking these supplements
need not fear adverse cardiovascul ar consequences whi le protecting their bone health.
Int. J. Cancer: 120, 1116-1122 (2006)
2006 Wiley-Liss. Inc.
The association of use of sunbeds with cutaneous malignant melanoma
and other skin cancers: A systematic review
The International Agency for Research on Cancer Working Group on artificial ultraviolet (UV) light and skin cancer
Exposure to solar ultraviolet (UV) radiation is a known cause of
skin cancer. Sunbed use represents an increasingly frequent
source of artificial UV exposure in light.-skinned populations. To
assess the available evidence of the association between sunbed
use and cutaneous malignant melanoma (melanoma) and other
skin cancers, a systematic r eview of the literature till March 2006
on epidemiological and biological studies on sunbed use was per-
formed in Pubmed, lSI Web of Scienc.e, Em base, Pascal , Cochrane
library, Lilacs and Medcarib. Search for keywords in the title and
in the abstract was done systematicall y and supplemented by man-
ual searches. Only case-control, cohort or cross-sectional studies
were selected. Data were abstracted by means of a standardized
data-collection protocol. Based on 19 informative studies, ever-use
of sunbeds was positively associated with melanoma (summary
relative risk, 1.15; 95% CI, 1.00-1.31), although there was no con-
sistent evidence of a dose-response relationship. First exposure to
sunbeds before 35 years of age significantly increased the risk of
melanoma, based on 7 informati ve studies (summary relative risk,
1.75; 95% CI, 1.35-2.26). The summary relative risk of 3 studies
of squamous cell carcinoma showed an increased risk. For basal
cell carcinoma, the studies did not support an association. The evi-
dence does not support a protective effect of the use of sunbeds
against damage to the skin from subsequent sun exposure. Young
adults should be discouraged from using indoor tanning equip-
ment and restricted access to sunbeds by minors should be
strongly considered.
2006 Wiley-Liss, Inc.
Key words: ;utificial UV; sunbeds; melanoma; skin cancer; meta-
analysis
Sun exposure is the main envi ronmental cause of skin cancer,
and ultraviolet (UV) radiation is the solar wavelength involved in
skin cancer, including the malignant cutaneous melanoma.
1
People
may also be exposed to UV radiation through many artificial sour-
ces at home and in the workplace, with some individuals receiving
high doses. Sources of artificial UV radiation include various lamps
used in medicine, industry, business and research, as well as for
domestic and cosmetic purposes. Sunbeds and sunlamps used for
tanning purposes are the main source of deliberate exposure to arti -
ficial UV radiation.t Although the contexts of sun exposure and
indoor tanning differ, both deliver UV radiation, and their health
effects would therefore be expected to be similar.
UV radiation wavelengths range between I 00 and 400 nm and
are broadly categorized into UVA (> 315-400 nm). UVB (>280-
315 run) and UVC (100-280 nm). Modern indoor tanning equip-
ment mainly emits in the UVA range, but a fraction (i.e . < 5%) of
this spectrum is in the UVB range.
Before 1990, UVB was usually considered the only ca.cino-
genic part of the solar spectrum, but since then UV A as well has
been suspected of having carcinogenic potential. In 1992, the
International Agency for Research on Cancer (IARC) classified
UVB and UV A radiation, as well as "use of sunlamps and sun-
beds," as " probably carcinogenic to humans" (Group 2A of the
IARC classification of carcinogenic agents). ' More recently, the
I Oth Report on Carcinogens published by the National Toxicology
Program in the USA classified UV A radiation as a "known to be a
human carcinogen. "
2
Biological mechanisms by which chronic
sun exposure causes squamous cell cancer (SCC) of the skin have
become better known and chronic exposure to high UVB doses is
now considered as the main environmental cause of that ski n
cancer.
3
Biological mechanisms implicated in basal cell carci-
~ u i
Publ ication of the International Union Against Cancer
noma (BCC) start to be better known. In contrast, we still have
poor knowledge of the UV wavelength and the dose delivery pat-
tern at skin level implicated in the genesis of melanoma and of
BCC.
4
Indoor tanning is widely practiced in most developed countries,
particularly in Northern Europe and the USA, and is 1.\aining popu-
larity even in sunny countries such as Australia.
6
The likely
impact of this fashion on skin cancer incidence is of substantial
concern, mainly for cutaneous malignant melanoma (hereafter
melanoma), a cancer of poor prognosis when diagnosed at an
advanced stage.
This paper summarizes a systematic review of epidemiological
and experimental studies on use of indoor tanning equipment and
skin cancer developed by a Working Group convened by IARC.
UV spectra from sunlight and indoor UV tanning appliances
During a sunny day on the Mediterranean coast, the solar UV
spectrum at noon contains 4-5% UVB and 95-96% UV A. When
UV output of a typical indoor tanning appliance is calculated in
terms of biological activity, as estimated by the erythema-effec-
tive inadiance, the emission of many tanning appliances is equiva-
lent to or exceeds the emission of the midday sun in southern
Europe.
7

8
The UV intensity of powerful tanning appliances may
be 10-15 times higher than that of the midday sun.
8
leading to
UV A doses per unit of time received by the skin during a typical
tanning session that are well above those experienced during ordi-
nary daily activities or even during sunbathing. As a result, the an-
nual UV A doses received by frequent indoor tanners may be 1.2-
4.7 times those received from the sun, in addition to those received
from the sun.
9
This widespread repeated exposure to high doses of
UV A constitutes a new phenomenon for human beings.
Members of the Working Group: Adele Green (Chair), Queensland
Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Qld,
Australia; Philippe Autier. Unit of Epidemiology. Prevention and Screen-
ing. Jules Bordet Institute, Brussels, Belgium (current address is: Interna-
tional Agency for Research on Cancer, Lyon, France); Mathieu Boniol and
Peter Boyle, International Agency for Research on Cancer, Lyon. France;
Jean-Francais DortS, INSERM U590, Centre Leon Berard, Lyon, France;
Sara Gandini, Division of Biostatistics and Epidemiology, European Insti -
tute of Oncology, Milan, Italy; Juli a Newwn-Bishop, Cancer Research UK
Genetic Epidemiology Division. St James's University Hospital , Leeds,
UK; Beatrice Secretan,* International Agency for Research on Cancer,
Lyon, France; Stephen J Walter, Cl inical Epidemiology and Biostatistics,
McMaster University, Hamilton, Ont., Canada; Martin A. Weinstock, Der-
matoepidemiology Unit, VA Medical Center, Providence, and Depan-
ments of Dermatology and Community Health, Brown University, Provi-
dence, Rhode Island; and Johan Westerdahl. Department of Surgery. Lund
University Hospital, Lund, Sweden.
tThe device used for tanning may be referred to as sunbed, sunlamp, ar-
tificial UV, artificial light or tanning bed. among other terms. Also, anum-
ber of terms are used to define a place where indoor tarming may occur: so-
larium, tanning salon, tanning parlor, tanning booth, indoor tanning salon,
indoor tanning facil ity. In addition, indoor tanning may also occur in non-
commercial premises. For the purpose of this report, the term indoor Ian-
ning equipment has been used throughout.
*Correspondence to: international Agency for Research on Cancer,
150 Cours Albert Thomas, F-69372 Lyon Cedex 08, France.
Fax: + 33-4-72738319 or +33-4-72738351. E-ma.il: secretan@iarc.fr
Received 8June 2006; Accepted after revision 27 September 2006
DOl 10. 1002/ijc.22453
Published online 27 November 2006 in Wiley lnterScience (www.interscience.
wiley.com).
SUNBED USE AND RISK OF MELANOMA AND SKIN CANCERS 1117
In the 1990s, regulations in some countries (e.g., France, Swe-
den) limited to 1.5% the maximum percentage of UVB in the UV
output of tanning appliances. However, in practice, the UV output
and spectral characteristics (i.e., amounts of UV A, UVB, visible
light and infrared radiation) of tanning appliances vary consider-
ably. The proportion of UVB in UV energy output could vary
from 0.5 to 4%,
10

11
and may attain an emission spectrum similar
to the sun spectrum in the UVB range.
8
These differences are due
to sunbed design (e.g., the numbers and type of fluorescent tubes,
the presence of high pressure UV lamps. the materials composing
filters, the distance from canopy to the skin), sunbed power and
tube ageing.
Biological effects of exposure to artificial UV radiation
relevant to carcinogenesis
A large body of experimental and epidemiological data strongly
indicates that the spectrum of l!,V radiation reaching the Earth's
surface causes skin cancer ...
12
.ao UVB is a complete carcinogen
that is absorbed by DNA and can damage DNA directly.
13
Evidence of the mutagenic properties of UV A in humans has
been found in several st udies.
12
-
14
UV A radiation does cause
UVB-like cyclobutane pyrimidine dimers and 6-4 photoproducts,
albeit with a much lower efficacy than does UVB radiation. Most
of the DNA damage induced by UV A is indirect, through the
absorption of UV A photons by other cellular structures (chromo-
phores), with formation of reactive oxygen species that can trans-
fer UV A energy to DNA via mutagenic oxidative intermediates.
15
Skin of human volunteers exposed to UV A lamps used in tan-
ning appliances show DNA damage, p53 mutations induced by
oxidative damage and alterations of the p53 protein similar to
those observed after sun exposure or after exposure of experimen-
tal animals.
1
6-
18
UV A penetrates deeper into human skin than does UVB.
Because UV A represents the largest proportion of the UV spec-
trum of tanning appliances and of solar radiation reaching the
Earth' s surface, far more UVA than UVB reaches the basal layers
of the epidermis where melanocytes and early keratinocytic cells
are located.
Both UV A and UVB radiation can affect the immune resrconse
that may be involved in the promotion of melanoma,'
5

19

0
but
the 2 types of radiation seem to act differentty_21.
22
UVB induces
immunosuppression at both the local and systemic levels, while
UV A does not induce systemic immune suppression
2 3
To date, evidence obtained from experimental studies on the
involvement of high UVB doses in the causation of SCC is con-
sistent with observations in htUnans. In contrast, experimental
studies give conflicting results regarding the roles of UVB and
UV A in the induction of melanoma in humans. The same uncer-
tainties hold true for BCC, a type of tumor that shares some epide-
miological characteristics of melanoma.
Experiments carried out in animals cannot reproduce the com-
plex interplay in individuals between highly variable natural sus-
ceptibilities to UV radiation, sun exposure behaviors and exposure
to various sources of UV radiation. During indoor tanning, such
interrelationships may be critical, as users are more inclined than
the average population to engage in outdoor tanning activities,
24
and indoor tanning sessions often precede or follow active sun ex-
posure or outdoor tanning.
Effects of artificial UV on human skin
Skin redness or burning are reported by 18-55% of users of
indoor tanning equipment in Europe and North America.
25
Although UVB is far more potent than UV A in causing sunburn,
high fluxes of UV A are capable of inducing skin redness in indi-
viduals sensitive to sunl ight or with only moderate tanning ability.
In individuals who tan easily, exposure to tanning appliances
will lead first to the oxidation of melanin already present in super-
ficial keratinocytic layers of the skin, known as immediate pig-
ment darkening?
6
A more permanent tan is acquired with accu-
mulation of exposure, depending on tanning ability and on the
amount of UVB present in the UV spectrum of the lamps.
Immediate pigment darkening has no photoprotective effect
against UV-induced skin redness or sunburn.
27
Moreover a OVA-
induced permanent tan provides little photoprotection
28

29
and the
skin thickening caused by UV A affords only very little photopro-
tection.30 Studies in humans show that a prevacation tan induced
artificially offers virtually no protection against sun-induced DNA
damage.:n-
33
E1posure to artificial UV for tanning pwposes
Few people had used indoor tanning equipment before 1980 but
by the end of the 1990s more than 60% of women and 50% of
men aged 18- 50 years in Northern Europe reported having ever
used indoor tanning equipment.
34
indeed, prevalence of indoor
tanning is increasing so rapidly in many countries that current esti-
mates may be outdated rapidly. The most frequent motivations for
indoor tanning are the acquisition of a so-called safe tan and prep-
aration of the skin before sun exposure.2
5
Use of indoor tanning equipment is more prevalent among
women and among both men and women younger than 35 years.
Earliest studies in Sweden and in the USA tended to find indoor
tanning to be more prevalent among adolescents with fair skin
types who are more prone to sunburn.
35
-
37
More recent studies in
the USA found either the opposite
38
-4 or no association.
4 1
Few studies have assessed the compliance of indoor tanning facil-
ity operators or consumers with recommendations and regulations.
Overall, information provided by tanning salon operators on health
risks and on duration and frequency of exposure is often incomplete,
and there is a lack of identification of highly sun-sensitive subjects or
of subjects taking photosensitizing medications.6.4
2
-44
About 17-35% sunbed users reported that they did not wear eye
protection.
10
.4
1

43
In some surveys, 16% of sunbed users may have
had more than I 00 sessions per year,
10
and most users tend to
exceed the recommended exposure times.
41

44

45
Since 1989, a total of 16 studies (18 reports) have examined
prevalence of indoor tanning among children and adolescents
aged 8- 19 years in Australia, Europe and the USA
46

47
All studies
showed a frequent use by adolescents and children, sometimes at a
very young age. According to the most recent studies, 30% of ado-
lescents in Sweden and 24% of adolescents in the USA aged 13-
19 years reported ever-use of indoor tanning equipment and 8 and
12% respectively were frequent users (10 times per year or more).
In a recent survey in the United Kingdom, while 7% of children
aged 8- 11 years reported exposure to a sunbed Ln the East 6
months, as many as 48% expressed a desire to use a sunbed.
8
Epidemiological studies on indoor tanning and skin cancer
As existing animal models of human melanoma are inconsis-
tent , evidence of an association between indoor tanning and skin
cancer must be sought predominantly from epidemiological stud-
ies. Few studies have addressed this topic specifically, but some
studies included I or more secondary questions about indoor tan-
ning. We systematically analyzed the results from the relevant
studies and compiled them in a metaanalysis.
Methods
The methodology used for the literature search is summarized
in Table I. The minimal common information about exposure to
indoor tanning appliances for all studies was "ever exposed. " For
those studies wherein "ever exposed to indoor tanning appliances
versus never" was not strictly assessed
4950
we used the informa-
tion closest to this category.
Most estimates included all subjects and combined sexes in the
analysis. Some studies presented results separately for women and
men, with no combined data, in which case both estimates were
1118 !ARC WORKING GROUP
included. Since the studies used different age categories for classi-
fying age at first exposure, we considered as " young exposure"
those exposures that started before 35 years of age.
Every measure of association adj usted for the maximum num-
ber of confounding variables, and corresponding confidence inter-
TABLE I- METHOD USED FOR THE LITERATURE SEARCH
The literature to March 2006 was searched using the following
databases: Pubmed, IST Web of Science (Science Citation
Index Expanded), Embase, Pascal, Cochrane library, Lilacs
and Medcarib. The following keywords and their
corresponding French translation were used for search in the
PASCAL database: skin cancer, squamous cell carcinoma,
SCC. basal cell carcinoma, BCC and melanoma for diseases.
To define exposure, the following keywords were used:
sunbed, sunlamp, artificial UV, artiflciallight, solaria,
solarium. indoor tanning, tanning bed, tanning parlour.
tanning salon and tanning booth.
Search for keywords in the title and in the abstract was done
systematically. Manual search was done of references cited in
the selected articles, and in selected reviews or books on
melanoma and skin cancer. All participants of the working
group were asked to report any additional published or
submitted study. No language restriction was applied.
Primary inclusion criteria were developed for the selection of
relevant articles, which were case-control, cohort or cross-
sectional studies published as an original article. Ecological
srudies. case reports, reviews and editorials were not
considered eligi ble.
The selected articles were reviewed, and data were abstracted by
means of a standardized data-collection protocol. When
another article on the same study was published
simultaneously, additional relevant or missing information
was retrieved from the companion paper.
val (CI), was transformed into logarithms of rela5ive risk (log RR)
and the corresponding variance was calculat.ed.'
1
Where no esti-
mates were reported, the crude estimates were calculated from
tabular data, using asymptotic Mantei-Haenszel methods to evalu-
ate the 95% CI of the log odds ratio.
The homogeneity of the effects across studies was assessed using
the large sample test based on the x.
2
-test. The summary relative risk
was estimated using random effects models even when heterogeneity
was found to be not statistically significant, in order to be conserva-
tive. Publication bias was investigated by funnel plot regression.
52
Studies on melanoma
We identified 23 studies on use of indoor tanning equipment
and melanoma (Table II) .
34
.4
9

50

5
3-
73
All studies used the case-
control design, except for I cohort studyso A case-control study
was considered population-based when cases were derived from a
population-based cancer registry and controls were selected from
the general population. Of these 23 studies, 4 studies were
excluded from the metaanalysis because they did not include esti-
mates of the relative risk for cutaneous melanoma associated with
exposure to tanning appliances.
53

5557

62
Studies used for the metaanalysis included a total of 7,355
cases. The first study was published in 1981 and the last in 2005.
Fifteen studies were carried out in European countries, 4 of which
in Scandinavian countries, and 2 were in the United States, I in
Canada and l in Australia.
Studies on basal cell and squamous cell carcinomas
Nine case-control studies have examined the association
between indoor tanning and either BCC or SCC of the skin.
7
4-8
2
All studies reported a risk estimate except one,
74
which was there-
fore excluded. A further 3 studies that did not distinguish between
TABLE n - CHARACTERISTICS OF THE STUDIES CONSIDERED FOR THE METAANALYSIS ON MELANOMA
Reference Coumry
Number
Relative risk
2
Cases Comrols
Cohort study _
Veier0d et al. (2003)'
0
Norway, Sweden 187 106.379
1
1.55 (1.04-2.32)
Population-based case-control
studies
Adam eta/. (1981)
54
UK 169 207 2.93 (l.l6-j.40)
Gallagher eta/. (l98<]t
5
Canada 595 595
Holman eta/. (1986)' Australia 511 511 1.1 (0.6-1.8)
Osterlind et al. (198ID
59
Denmark 474 926 0.73 (0.53-1.01)
Zanetti eta/. (1988) Italy 208 416 0.9 (0.4- 2p)
Beitner eta/. (1990)
62
Sweden 523 505
Walter et a/. (1990)
63
Canada 583 608
4
Westerdahl et al. (1994)
70
Sweden 400 640 1.3 (0.9-1.8)
Holly era/. USA 452 930 0.94 (0.74-1.2)
Chen era/. (1998)
69
USA 624 512 1.13 (0.82-1.54)
Walter eta/. (1999)
64
Canada 583 608 !.54 ( 1.1 6-2.05)
Westerdahl era/. (2000)
73
Sweden 571 913 1.2 (0.9-1.6)
Other case-control studies
Klepp and Magnus

Norway 78 131
Holly er a/. ( 1987)
5
USA 121 139
Swerdlow eta/.

UK 180 120 2.94 (1.41- 6.17)
MacKie et a/. ( 1989)
6
UK 280 !80 1.3 (0.2-7.9) for men;
Dunn-Lane et al. (1993)
65
1.2 (0.5-3.0) for women
UK 100 100 1.16 (0.54-2.47)
Garbe eta/. (1993)
66
Germany 280 280 1.5 (0.9-2.4)
Autier eta/. (

Belgium, France, and Germany 420 447 0.97 (0.71-1.32)
Naldi eta/. (2000)
1
Italy 542 538 0.78 (0.45- 1.37)
Kaskel eta/. (2001)
49
Germany 271 271 1.00 (0.6-1.8)
Bataille eta/. (2004)
72
UK 41 3 416 1. 19 (0.84-1.68)
Bataille eta/. (2005)
34
Belgium, France, the Netherlands, 597 622 0.90 (0.71-1.14)
Sweden, UK
ALM, acrallentiginous melanoma; HC, histologically confirmed; LMM, lentigo maligna melanoma; M, melanoma; MM, malignant melanoma;
NM, nodular melanoma; SSM, superficial spreading melanoma.
1
Cohort size.-
2
Values in parentheses are 95% CI .-
3
Because no estimate of risk was reported in these studies, we did not include them in the
metaanalysis.-
4
The study by Walter et al. (1990)
63
was reanalyzed in the 1999 publication. We used the relative risk adjusted for potential con-
founders presented in the 1999 publication.
SUNBED USE AND RISK OF MELANOMA AND SKIN CANCERS 1119
Studies
Adam et e.!.,
Holnwl et e.!., I
OsterliM et e.!, 1988
Swerdlow et e.!, 1988
Zanetti et e.!., 1988
MeeK ill et e.!., I (Men)
MIIC.Kie et al, 1989 (Women)
Dunn-!..an et e.l.,l993
Geroe et e.!., 1993
A ulier et e.!., 1994
WesteldAhl et e.!., 1994
Holly et e.!., 199 5
Chen et e.!.,
Welter et e.!., 1999
N eldi et e.!., 2000
WesteldAhl et e.!., 2000
Keske! et e.!, llDI
Veierod et e.!., 2003
Bataille et e.!., 2004
&taille et e.!., 2005
Summary relative risk
-
-
-
--
I
-
-

-
p
1.15 (1.00, 1.31)
I I I I I I
0.5 1.0 1.5 2.0 2.5 3.0 5.0 7.0
FIGURE 1 - Relative risk for cu-
taneous melanoma associated with
ever use of indoor tanning equip-
ment: estimates of 19 studies and
summary estimate (relative risks
were presented separately for men
and women in the study by
MacKie et a/
61
) . Relative risk
TABLE Ill - METAANALYSIS OF EPIDEMIOLOGICAL STUDIES ON INDOOR TANNING AND RISK
FOR J'vlELANOMA, SQUAMOUS CELL CARCINOMA AND BASAL CELL CARCINOMA
Exposure
Number of
Summary relative risk
1
Heterogeneity
2
sludics (pvalue)
Melanoma
Ever use of indoor tanning equipment 19 1.15 (1.00-1.31) 0.013
First exposure in youth 7 1.75 ( 1.35-2.26) 0.55
Exposure distant in time 5 1.49 (0.93- 2.38) 0.018
Exposure recent in time 5 1.10 (0.76-1.60) 0.81
Squamous cell carcinoma
Ever use of indoor tanning equipment 3 2.25 (1.08-4.70) 0.10
Basal cell carcinoma
Ever use of indoor tanning equipment 4 1.03 (0.56-1. 90) 0.06
1
Values in parentheses are 95% CI.-
2
x
2
-test: the degrees of freedom are given by the number of risk
estimates included minus I.
these 2 major types of skin cancer
75
-
77
were also excluded from
review, leaving 5 studies for consideration.
Relative risk for melanoma
Thirteen of 19 studies presented positive estimates for "ever"
versus " never" exposed to inc_loor tanning equipment, but only 4
were statistically


(Fig. 1). Seven of these stud-
ies reported only crude relative risks, and I adjusted for age and
sex only. Results of the metaanalysis are shown in Table III. The
summary estimate indicated a significant positive association
between "ever" versus "never" indoor tanning and melanoma
(RR, 1.15; Cl, 1.00-1.31) and the x
2
-test for heterogeneity was
statistically significant.
To decrease the influence of possible biases, estimates were cal -
culated including only the cohort and the 9 population-based
case-control studies. The sununary relative risk was very similar
apart from having wider Cis (RR, 1.17; CI, 0.96-1.42).ln an anal-
ysis restricted to the 8 studies that adjusted for confounders related
to sun exposure and sun sensitivity,
0

60

6
1.
64

69
-
7
1.
73
the summary
relative risk remained simi lar to that obtained from all 19 studies,
but the CI widened (RR. 1.19; CI, 0.33-4.30).
Seven studies presented estimates relevant for the evaluation of
" first exposure in youth" versus " never" (Fig. 2). All relative
risks were adjusted for confounders related to sun exposure or sun
sensitivity, except in the study by Walter e t a/
64
A sini ficant
75% increase in risk was detected (Table liT) and the X -test for
heterogeneity was nonsignificant.
Five studies investigated time since exposure and reported esti-
mates that a.llowed comparisons between recent and more distant
exposure.
34

58

63

67

69
Metaanalytic estimates were greater for
exposures more distant in time when compared to those for more
recent exposures (Table III).
There was some indication for a dose-effect relationship in 2
studies,
67

70
but not in the other two.
69

73
But metrics used for
assessing duration were all different and therefore did not permit
met.aanalytic synthesis. Only 4 studies explored the role of natural
sensitivity to sunlight on risk associated with indoor tanning, and
overall, they found no consistent resuJt.
34

64
72.
73
Type of indoor tam1ing equipment
No epidemiological study has been able to explore in a rigorous
way amounts of UV A and UVB received by indoor tanning users.
The study by Chen et a/.
69
obtained information concerning the
type of sunbed or sunlamp used (e.g. , desktop models, floor mod-
els, beds or walk-in booths). This information was obtained by
showing to subjects pictures of various types of sunlamps and sun-
1120 !ARC WORKING GROUP
Studies
Swerdlow et. al, 1988
Westerdahl et al., I 994
Chen et al. , 1998
Walter et a1 , 1999
Westerdahl et al., 2000
Veierod et al, 2003
Bataille et al., 2005
Summary relative risk
FIGURE 2- Relative risk for cu-
taneous melanoma associated with
first use of indoor tanning equip-
ment at age <35 years: estimates of
7 studies and summary estimate.
beds. The study found a nonsignificant elevated risk of malignant
melanoma associated with the use of desktop sunlamps and heavy-
weight floor-model sunbeds and a statistically significant tripled
risk associated with use of more than 2 types of sunlamps, com-
pared with no use of sunbeds. The study by Bataille et a/.
34
reported no impact of the type of device used on melanoma risk.
The relative risks of melanoma associated with ever-use of
sunbed/sunlamp reported in the studies did not vary with year of
publication or first year of study period, and funnel plot regression
gave no indication of publication bias (ever-use of sunbed/sun-
lamps, p = 0.80; first exposure in youth, p = 0.10). This observa-
tion suggests that the apparent increased risk for ever use and for
age at first use were unlikely to be explained by the earlier types
of indoor tanning appliance used.
Before 1980, exposure to artificial UV radiation was more
likely to take place at home with devices that emitted greater
amounts of UVB radiation, whereas exposure in the 1980s
increasingly occurred in commercial salons using equipment that
emitted mainly UVA. The Norway- Swedish prospective study
provided evidence that the increased melanoma risk associated
with exposure to t n n i n ~ appliances was not due to the type of UV
lamps used before 1983.
3
Relative risk for squamous cell carcinoma
and basal cell carcinoma
The metaanalysis was based on the 5 studies
78
-8
2
reporting type-
specific risk estimates (Table III). Metaanalytic estimates suggested
a significant effect of exposure to indoor talUling appliances for
SCC, but not for BCC. Funnel plot regression gave no indication of
publication bias (p = 0.26 and 0.77 for SCC and BCC, respec-
tively).
The study by Karagas et al.x
1
gave the most detailed results,
and the trends were consistent with the results reported for mela-
noma. Results were adjusted for sun sensitivity but not for sun ex-
posure, since adjustment for sun exposure did not change the risk
estimates. Depending on age at first use, the risks for BCC and
SCC were found to increase by 10% (OR, 1.1; Cl, 0.9-1.5) and
20% (OR, 1.2; CI, 0.9-1.6) respectively for each decade younger
the person was at first use of indoor tanning equipment.
-
-

-
-

-
<>
1.75 (1.35-2.26)
I I I I I I I
0.5 1.0 1.5 2.0 2.5 3.0 5.0 7.0
Relative risk
Discussion
Investigation of the assoc1atwn between indoor tanning and
skin cancers poses challenging problems, as indoor tanning has
been in widespread use only recently. Based on our knowledge
about the relationship between sun exposure and ri sk for mela-
noma, it could be stated that associations after long latency peri-
ods, such as would be expected for melanoma and BCC, may not
be detectable yet. Also, since the fashion of indoor tanning has
been increasing steadily, the failure to distinguish between distant
and recent exposures in most epidemiological studies may mask
an actual increase in risk with exposure early in life.
Our systematic review of published studies mainly from Europe
and North America of the association of use of indoor tanning
equipment with skin cancers revealed an association of age at first
use of less than 35 years with melanoma risk. These studies consis-
tently indicated a moderate strength of association, with a summary
relative risk of 1.75 (1.35-2.26). This result suggests a greater vul-
nerability of younger people to the carcinogenic impact of indoor
tanning. Also, it is in agreement with the knowledge that age at ex-
posure may influence the relative risk for skin cancer associated
with UV exposure, and that exposure to sunlight in childhood is an
important contributing factor for melanoma risk in adults.
84

85
The association with ever-use of such equipment, or use more
than '15- 20 years prior to diagnosis of melanoma. was weak, and
evidence regarding a dose- response relationship was scant. The
evidence is limited by concerns over characterization of exposure
and recall of exposure by individuals, potential confounding by
sun exposure or other variables and the low power to dete.ct asso-
ciations that become evident only following a prolonged lag pe-
riod after exposure. Our results are similar to a previous metaanal-
ysis,86 but our systematic review is more exhaustive and included
more studies.
In Scandinavian countries use of indoor tanning equipment has
been popular since the late 1970s and the prevalence of use in
those countries is the highest in the world. In the Norwegian-
Swedish prospective study the highest risk for melanoma was
found in women who used indoor tanning equipment at least once
per month when they were 20- 29 years old. These results support
the hypothesis that a certain lag period is needed before the impact
SUNBED USE AND RISK OF MELANOMA AND SKIN CANCERS 1121
of exposure to tanning appliances on melanoma incidence
becomes apparent. It also underlines the greater vulnerability of
younger subjects to harmful effects of indoor tanning.
The positive association between use of indoor tanning equip-
ment and melanoma risk reported here is consistent with the
knowledge that melanoma is caused primarily by exposure to solar
radiation. The limited evidence for a positive association between
indoor tanning and sec is consistent with its known dependence
on dose of UV radiation to the skin. Thus the biological plausibil -
ity of a causal association between indoor tanning and risk for
melanoma and sec is strong.
On balance, the evidence pertaining to the strength, consistency,
dose- response and temporal sequence of the association of the use
of indoor tanni ng equipment with melanoma risk, and of the coher-
ence and biologic plausibility of the association, leads us to conclude
that there is convincing evidence to support a causal relationship,
particularly with exposwe before the age of 35 years. This evidence
is strongly suggestive and further studies could clarify our under-
standing of tllis association and allow more definitive conclusions.
We are cognizant of the importance of this issue for the health
of light-skinned populations. The strength of the existing evidence
suggests that policy makers should strongly consider enacting
measures such as restricting minors and discouraging young adults
from using indoor tanning equipment, in order to protect the gen-
eral population from additional risk for melanoma and squamous
cell skin cancer.
References
l. IARC. Solar and ultraviolet radiation. Lyon: International Agency for
Research on Cancer, 1992. !ARC monographs on the evaluation of
carcinogenic risks to humans , vol. 55.
2. National Toxicology Program. lOth Report on Carcinogens: substan-
ces profiles. Research Triangle Park, US Department of Health and
Human Services, Public Health Service, 2002.
3. de Gruijl FR, van Kranen HJ, Mullenders LH. UV-induced DNA
damage, repair, mutations and oncogenic pathways in skin cancer.
1 Photochem Photobiol B 2001 ;63:19- 27.
4. de Gruijl FR. Photocarcinogenesis: UVA vs. UVB radiati on. Skin
Pharmacol Appl Skin Physiol 2002; 15:316- 20.
5. Paul CL, Girgis A, Tzelepis F, Walsh RA. Solaria use by minors in
Australia: is there a cause for concern? Aust. N Z J Public Health 2004;
28:90.
6. Paul CL, Stacy F, Girgis A. Brozek I, Baird H, Hughes J. Solaria com-
pliance in an unregulated environment: the Australian experience. Eur
1 Cancer 2005:41 :1178- 84.
7. Wester U. Boldemann C, Jansson B, Ullen H. Population UV-dose
and skin area-do sunbeds rival the sun? Health Phys 1999;77:436-
40.
8. Gerber B, Mathys P, Moser M, Bressoud D, Braun-Fahrlander C.
Ul traviolet emission spectra of sunbeds. Photochem Photobiol 2002;
76:664-8.
9. Miller SA, Hamilton SL, Wester UG, Cyr WH. An analysis of UV A
emissions from sunlamps and the potential importance for melanoma.
Photochem Photobiol 1998:68:63-70.
10. MacGintley J, Manin CJ, MacKie RM. Sunbeds in currem use in
Scotland: a survey of their output and pattems of use. Br J Dermatol
1998:139:428-38.
II. Wrigllt AL, Hart GC, Kernohan E, Twentyman G. Survey of the vari-
ation in ultraviolet outputs from ultraviolet A sunbeds in Bradford.
Photodermatol Photoimmunol Photomed 1996; 12: 12- 16.
12. Pfeifer GP, You YH, Besaratinia A. Mutations induced by ultraviolet
light. Mutat Res 2005:571:19-31.
13. Griffiths HR, Mistry P, Herbe rt KE. Lunec J. Molecular and cellular
effects of ultraviolet light-induced genotoxicity. Crit Rev Clin Lab
Sci 1998;35: 189- 237.
14. Robel'! C, Muel B, Benoit A, Dubertret L, Sarasin A, Stary A. Cell
survival and shullle vector mutagenesis induced by UV A and UVB
radiation in a human cell line. J Invest Demtatol 1996; 106:721-8.
15. Halliday G. Inflammation, gene mutation and photoimmunosuppres-
sion in response to UVR-induced oxidative damage contributes to
photocarcinogenesis. Mut Res 2005;571: I 07-20.
16. Woollons A, Clingen PH, Price ML, Arlett CF, Green MH. Induction
of mutagenic DNA damage in human fibroblasts after exposure to ar-
tificial tanning lamps. Br J Dermatol1997;137:687-92.
17. Whitmore SE, Morison WL, Potten CS, Chadwick C. Tanning salon
exposure and molecular alterations. J Am Acad Dermatol 2001:44:
775-80.
18. Persson AE, Edstrom DW, Backvall H, Lundeberg J, Ponten F, Ros
AM, Williams C. The mutagenic effect of ultraviolet-A I on human
skin demonstrated by sequencing the p53 gene in single kerat inocytes.
Photodermatol Photoimmunol Photomed 2002; 18:287- 93.
19. Kripke ML. Antigenicity of murine skin tumors induced by UV light.
J Nat ! Cancer Inst 1974:53: 1333-{).
20. Singh RK, Gutman M, Reich R, Bar-Eli M. Ultraviolet B irradiation
promotes tumorigenic and metastatic properties in primary cutaneous
melanoma via induction of interleukin-8. Cancer Res 1995;55:3669-
74.
21. Phan TA, Halliday GM. Barnetson RS, Damian DL. Spectral and
dose dependence of ultraviolet radiation-induced immunosuppression.
Front Biosci 2006: I I 9 ~ 11.
22. Aboutalebi S, Strickland FM. lmmune protection, natural products,
and skin cancer: is there anything new under the sun? J Drugs Derrna-
tol2006;5:512- 7.
23. Ullrich SE. Mechanisms underlying UY-induced immune suppres-
sion. Mutat Res 2005:571:185-205.
24. Autier P, Joarlette M. Lejeune F. Lienard D, AndreJ, Acbten G. Cuta-
neous malignant melanoma and exposure to sunlamps and sunbeds: a
descriptive study in Belgium. Melanoma Res 1991; I :69-74.
25. Autier P. Perspectives in melanoma prevention: the case of sunbcds.
Eur J Cancer 2004;40:2367-76.
26. Pedeux R, AI-Irani N, Maneau C, Pellicier F, Bra11che R, Ozturk M,
Franchi J, Dore JF. Thymidine dinucleotides induceS phase ce ll cycle
arrest in addition to increased melanogenesis in human melanocytes.
1lnvest Dermatoll998; 111:472-7.
27. Black G, Matzinger E. Gange RW. Lack of photoprotection against
UVB-induced erythema by immediate pigmentation induced by 382
nm radiation. J Invest Dermatoll985:85:448- 9.
28. Gange RW, Blackett AD, Matzinger EA, Sutherland BM, Kochevar
IE. Comparative protection efficiency of UVA- and UVB-induced
tans against e rythema and formation of endonuclease-sensitive sites
in DNA by UVB in human skin. J Invest Dermatol l 985;85: 362-4.
29. Rivers JK, Norris PG, Murphy GM, Chu AC. Midgley G, Morris J,
Morris RW, Young AR, Hawk JL UV A sunbeds: tanning, photopro-
tection, acute adverse effects and immunological changes. Br J Der-
matol 1989; 120:767-77.
30. Sheehan JM. Potten CS, Young AR. Ta1ming in human skin types ll
and m offers modest photoprotection against erythema. Photochem
Photobiol 1998;68:588- 92.
31 . Hemminki K, Bykov V J, Marcusson JA. Re: Sunscreen use and dura-
tion of sun exposure: a double-blind, randomised trial. 1 Nat! Cancer
lost 1999;91 :2046-7.
32. Bykov VJ, Marcusson JA, Hemminki K. Protective effects of tanning
on cutaneous DNA damage in s itu melanoma. Dermatology 200 I ;
202:22- 6.
33. Ruegemer J. Schuetz B, Hermann K, Hein R, Ring J, Abeck D. UV-
induced skin changes due to regular use of commercial sunbeds. Pho-
todermatol Photoimmunol Photomed 2002; 18:223- 7.
34. Bataille V, Boniol M, De Vries E, Severi G, Brandbcrg Y, Sasieni P,
Cuzick J, Eggermont A, Ringborg U. Grivegnee AR, Coebergh JW.
Chignol MC, et al. A multicentre epidemiological study on sunbed
use and cutaneous melanoma in Europe. Eur J Cancer 2005;41:2141- 9.
35. Me1melstein RJ, Riesenberg LA. Changing knowledge and attitudes
about skin cancer risk factors in adolescents. Health Psycho! 1992:
11:371- 6.
36. Boldeman C, Beitner H, Jansson B, Nilsson B, Ullen H. Sunbed use
in relation to phenotype, erythema, sunscreen use and skin diseases. A
questionnaire survey among Swedish adolescents. Br J Dermatol
1996; 135:712-6.
37. Robinson JK, Rademaker AW, Sylvester JA, Cook B. Summer sun
exposure: knowledge, attitudes and behaviors of Midwest adolescents.
Prev Med 1997;26:364-72.
38. Cokkinides VE, Weinstock M, O' Connel l MC, Thun MJ. Use of
indoor tanning sunlamps by US youth, ages 11- 18 years, and by their
parent or guardian caregivers: prevalence and correlates. Pediatrics
2002; 109: 1124-30.
39. Demko CA. Borawski EA, Debanne SM. Cooper KD, Stange KC.
Use of indoor tanning faci lities by white adolescents in the United
States. Arch Pediatr Adolesc Med 2003;157:854-60.
40. Geller AC, Colditz GA. Oliveria S, Emmons K. Jorgensen C, Aweh
GN, Frazier AL. Use of sunscreen, sunburning rates, and tanning bed
use among more than 10,000 US children and adolescents. Pediatrics
2002; 109: 1009-14.
1122 !ARC WORKING GROUP
41. Oliphant JA, Forster JL, McBride CM. The use of commercial tanning
fac ilities by suburban Minnesota adolescents. Am J Public Health
1994;84:476- 8.
42. Culley CA. Mayer JA, Eckhardt L, Busic A.l , Eichenfield LF, Sall is
JF, Quintana PJ, Woodmff SI. Compliance with federal and state
legislation by indoor tanning facilities in San Diego. J Am Acad Der-
matol 200 I ;44:53-60.
43. Rhainds M, De Guire L, Claveau J. A population-based survey on the
use of artificial tanning devices in the province of Quebec, Canada.
J Am Acad Dcm1atol 1999;40:572-6.
44. Kwon HT, Mayer JA, Walker KK. YuH. Lewis EC. Belch GE. Pro-
motion of frequent tanning sessions by indoor tanning facilities: two
studies. JAm Acad Dermatol 2002;46:700-5.
45. Hornung RL, Magee KH, Lee WJ, Hansen LA. Hsieh YC. Tanning
facility use: are we exceeding Food and Drug Administration limits?
JAm Acad Dennatol2003;49:655-61.
46. Lazovich D, Forster JL, Sorensen G, Emmons K, Stryker JE, Demi-
erre MF, Hickle A, Remba N. Characteristics associated with use or
intention to use indoor tanning among adolesceots. Arch Pediatr Ado-
lese Mcd 2004;158:918- 24.
47. Lazovich D, Forster J. lndoor tanning by adolescents: prevaleoce.
practices and policies. Eur J Cancer 2005;41:20-7.
48. Hamlet N, Kennedy K. Reconnaissance study of sunbed use by pri-
mary school children in Lanarkshire. J Public Health 2004;26:31-3.
49. Kaskel P, SanderS, Kron M, Kind P, Peter RU, Krahn G. Outdoor
activities in childhood: a protective factor for cutaneous melanoma?
Results of a case-control study in 271 matched pairs. Br J Dermatol
2001; 145:602-9.
50. Veieri'Sd MB, Weiderpass E, Thorn M, Hansson J, Lund E, Armstrong
B, Adami HO. A prospective study of pigmentation, sun exposure,
and risk of cutaneous malignant melanoma in women. J Nat! Cancer
Inst 2003;95: I 530-8.
51. Greenland S. Quantitative methods in the review of epidemiologic lit-
erature. Epidemiol Rev 1987;9:1-30.
52. Macaskill P, Walter SD, Irwig L. A comparison of methods to detect
publication bias in meta-analysis. Stat Med 2001 ;20:641-54.
53. Klepp 0 , Magnus K. Some environmental and bodily characteristics
of melanoma patients. A case-control study. lnt J Cancer 1979;23:
482-6.
54. Adam SA, Sheaves JK, Wright NH, Mosser G, Harris RW, Vessey
l\tiP. A case-control study of the possible association between oral
contraceptives and malignant melanoma. Br J Cancer 1981 ;44:45-
50.
55. Gallagher RP. Elwood JM, Hill GB. Risk factors for cutaneous malig-
nant melanoma: the Western Canada Melanoma Study. Recent
Results Cancer Res 1986;102:38- 55.
56. Holman CD, A1111st rong BK, Heenan PJ, Blackwell JB, Cumming FJ,
Engl ish DR, Holl and S, Kelsall OR, Matz LR. Rouse IL, Singh A,
Ten Seldam REJ et al. The causes of malignant melanoma: results
from the West Austral ian Lions Melanoma Research Project. Recent
Results Cancer Res 1986;102:18- 37.
57. Holly EA, Kelly JW, Shpall SN. Chiu SH. Number of melanocytic
nevi as a major risk factor for mal ignant melanoma. J Am Acad Der-
matol 1987; 17:459-68.
58. Swerdlow AJ, English JS, MacKie RM, O' Doherty CJ, Hunter JA,
Clark J, Hole DJ. Fluorescent lights, ultraviolet lamps, and risk of cu-
taneous melanoma. Br Med J 1988;297:647-50.
59. Osterlind A. Tucker MA, Stone BJ, Jensen OM. The Danish case-con-
trol study of cutaneous malignant melanoma. II. Importance of UV-
light exposure. lnt J Cancer 1988;42:319-24.
60. Zanetti R. Rosso S, Faggiano F. Roffino R, Colorma S, Martina G. A
case-control study on cutaneous mal ignant melanoma in the province
of Torino, Italy. Rev Epidemiol Sante Publique 1988;36:309- 17 [in
French].
61. MacKie RM, Freudenberger T, Aitchison TC. Personal risk-factor
chart for cutaneous melanoma. Lancet 1989;2:487- 90.
62. Beitner H. Norell SE, Ringborg U. Wennersten G, Mattson B. Malig-
nant melanoma: aetiological importance of individual pigmentation
and sun exposure. Br J Dermatoll990;122:43- 51.
63. Walter SD, Marrett LD, From L, Hertzman C, Shannon HS, Roy P.
The association of cutaneous malignant melanoma with the use of
sunbeds and sunlamps. Am J Epidemioll990;131:232-43.
64. Walter SD, King WD, Marrett LD. Association of cutaneous malig-
nant melanoma with intermittent exposure to ultraviolet radiation: re-
sults of a case-control study in Ontario, Canada. lnt J Epidemiol 1999;
28:418- 27.
65. DUim-Lane J. Herity B, Moriarty MJ, Conroy R. A case control study
of malignant melanoma. lr Med J 1993;86:57-59. Erratum in: lr Med
J 1993;86: 135.
66. Garbe C, Weiss J, Kruger S, Garbe E, Buttner P, Bertz J, Hoffmeister
H, Guggenmoos-Holzmann I, Jung EO, Orfanos CE. The German
melanoma regist ry and environmental risk factors implied. Recent
Results Cancer Res 1993; 128:69- 89.
67. Autier P. Dore JF, Lejeune P, Koelmel KF, Geffe ler 0 , Hille P, Cesar-
ini JP, Lienard D, Liabeuf A, Joarlette M, ChemaJy P, Hakim K, ct al.,
for the EORTC Melanoma Cooperative Group. Cutaneous malignant
melanoma and exposure to sunlamps or sunbeds: for the EORTC mul-
ticenter case-control study in Belgium, France and Germany. lnt J
Cancer 1994;58:809-13.
68. Holly EA, Aston DA, Cress RD, Ahn DK, Kristiansen JJ. Cutaneous mel-
anoma in women. T. Exposure to sunlight, ability to tan, and other risk
factors related to ultraviolet light. Am J Epidemiol 1995; 141 : 923- 33.
69. Chen YT. Dubrow R, Zheng T. Barnhill RL, Fine J, Berwick M. Sun-
lamp use and the risk of cutaneous malignant melanoma: a popula-
tion-based case-control study in Connecticut, USA. Int J Epidemiol
1998;27:758-65.
70. Westerdabl J, Olsson H. Masback A, Jngvar C. Jonsson N, Brandt L,
Jonsson PE, Moller T. Use of sunbeds or sunlamps and malignant
melanoma in southem Sweden. Am J Epidemiol 1994; 140:691- 9.
71. Naldi L, Gall us S, Imberti GL, Cainelli T, Negri E, LaVecchia C, on
behalf of the Italian Group for Epidemiological Research in Derma-
tology. Sunlamps and sunbeds and the risk of cutaneous melanoma.
Eur J Cancer Prev 2000;9: 133-4.
72. Bataille V, Winnett A, Sasieni P, Newton-Bishop JA, Cuzick J. ExpO-
sure to the sun and sunbeds and the risk of cutaneous melanoma in the
UK: a case-control study. EUI J Cancer 2004;40:429-35.
73. Westerdahl J, Ingvar C, Masback A, Jonsson N, Olsson H. Risk of cu-
taneous mali gnant melanoma in relation to use of sunbeds: fu rther
evidence for UV-A carcinogenicity. Br J Cancer 2000;82: 1593- 9.
74. Boyd AS, Shyr Y, King LE Jr. Basal cell carcinoma in young women:
an evaluation of the association of tanning bed use and smoking.
JAm Acad Dermatol
75. O'Loughlin G, Moriarty MJ, Herity B, DaJy L. A re-appraisal of risk
factors for skin carcinoma in Ireland. A case-control study. Ir J Med
Sci 1985; 154:61-5.
76. Heri ty B. O'Loughlin G, Moriarty MJ. Conroy R. Risk factors for
non-melanoma skin cancer. J lr Med 1989;82: 151-2.
77. Hogan DJ, ToT. Wilson ER, Miller AB, Robson D, Holfeld K, Lane
P. A study of acne treatments as risk factors for skin cancer of the
head and neck. Br J Dermatol l991;125:343-8.
78. Aubry F. MacGibbon B. Risk factors of squamous cell carcinoma of
the skin. A case-control study in the Montreal region. Cancer 1985;
55:907-11.
79. Bajdik CD, Gallagher RP, Astrakianakis G, Hill GB, Fincham S,
McLean Dl. Non-solar ultraviolet radiation and the risk of basal and
squamous cell skin cancer. Br J Cancer 1996;73: 1612-4.
80. Corona R, Dogliotti E, D'Errico M, Sera F. Iavarone I, Baliva G,
Chinni LM, Gobello T, Mazzanti C, Puddu P, Pasquini P. Risk factors
for basal cell carcinoma in a Mediterranean population: role of recrea-
tional sun exposure early in li fe. Arch Dermatol 2001; 137: 1162-8.
81. Karagas MR, Stannard VA, Mott LA, Slattery MJ, Spencer SK, Wein-
stock MA. Use of tanning devices and risk of basal cell and squamous
cell skin cancers. J Nat! Cancer Inst 2002;94:224-6.
82. Walther U, Kron M, Sander S, Sebastian G, Sander R, Peter RU,
Meurer M, Krdllll G, Kaskel P. Risk and protective factors for spo-
radic basal cell carcinoma: results of a two-eentre case-control study
in southern Germany. Clinical actinic elastosis may be a protective
factor. Br J Dennatol2004;151:170-8.
83. Veier0d MB, Weiderpasss E, Lund E, Armstrong BK, Adami HO.
Re: A retrospective study of pigmentation, sun exposure, and risk of
cutaneous malignant melanoma in women. J Nat! Cancer lnst
2004;96:337-S.
84. Autier P, Dare JF, for EPIMEL and EORTC Melanoma Cooperative
Group. Influence of sun exposures during childhood and during adult-
hood on melanoma risk. Int .I Cancer 1998;77:533- 7.
85. Whiteman DC, Whiteman CA. Green A. Childhood sun exposure as a
risk factOr for melanoma: a systematic review of epidemiologic stud-
ies. Cancer Causes Control 200 l ; 12:69-82.
86. Gallagher RP, Spinell i JJ, Lee TK. Tanning beds, sunlamps, and risk
of cutaneous mal ignant melanoma. Cancer Epidemiol Biomarkers
Prev 2005; 14:562-6.
News I
Special Report: Policy
A review of human carcinogens-Part D: radiation
In June 2009, 20 scientists from nine
countries met at the International
Agency for Research on Cancer (IARC)
to reassess the carcinogenicity of the
types of radiation previously classified
as "carcinogenic to humans" (Group 1)
and to ident ify additional tumour sites
and mechani sms of carcinogenesis
(table and panel). These assessments
wil l be published as part D of Volume
100 ofthe I ARC Monographs.'
Alpha particles, consisting of two
protons and two neutrons, are a
densely ionising type of radiat ion
wi th low capaci ty to penet rate living
tissue (less than 0-1 mm). Beta
particles are electrons or positrons
that are less ionising, but more
penetrating (up to a few milimetres).
The health hazards resulting from
radionuclides that emit these
particles largely occur after internal
deposition. Epidemiological evidence
shows a number of radionuclides that
emit alpha or beta particles increase
cancer risks at several anatomical sites
(table). The Worki ng Group reaffirmed
the carcinogenicity of internally
deposited radionuclides that emit
alpha or beta particles (Group 1).
Radiation type
Alpha-particle and beta-particle emitters
After the Chernobyl accident. a
sharp increase in the risk of thyroid
cancer was found with exposure to
radioiodines, particularly iodine-131,
during chi ldhood and adolescence.u
This increased risk might be due to
higher milk intake per unit of body
weight among chi ldren; a higher thyroid
dose per unit of iodine-131 intake from
milk; a higher susceptibility per unit of
thyroid dose; or a combination of these.
Radon exposure occurs mainly
through contamination of indoor
air by radon released from soil and
building materials. Combined analyses
of case-control studies now estimate
that residential exposure to radon gas
is the leading cause of lung cancer after
tobacco smoke (8-15% attributable
risk in Europe and North America).-
5
X-rays and gamma-rays are
sparsely ion1smg electromagnetic
radiation that penetrate living tissue,
typical ly producing fast electrons that
deposit energy, resulting in tissue
damage. Extensive study of atomic-
bomb survivors shows increased
cancer risks at multiple anatomical
sites.
6
Current evidence adds to the
list of tumours caused by x-rays
Major study populations
and gamma-rays (table), and also
establishes that in-utero exposure
increases the risk of cancer at multiple
sites.
7

8
The Working Group reaffirmed
the carcinogenicity of x-radiation and
gamma-radiation (Group 1).
Neutrons are produced by nucl ear
reactions and are a main component
of cosmic radiation. They are highly
penetrating and interact with
the t raversed tissue, producing
protons, other charged part icles, and
gamma-radiation. Epidemiological
evidence is inadequate to assess the
carcinogenicity of neutrons, because
of co-exposures to other types of
radiation. However, the evidence
of cancer in experimental animals
is sufficient, and mechanistic data
show that neutrons t ransfer their
energy in clusters of ionising events-
resulting in similar, but more severe,
local damage than that induced by
x-rays or gamma-rays. On the basis
of this evidence, the Working Group
reaffirmed the carcinogenicity of
neutron radiation (Group 1).
Each type of ionising radiation
(panel) transfers energy in the
form of highly structured tracks of
Upcoming meetings
Sept 29-0ct 6, 2009
Lifestyle Factors
Oct 20-27, 2009
Chemical Agents and Related
Occupations
http://monographs.iarc.fr/
Tumour sites (and types) on which sufficient evidence is based
Radon-222 and decay products General population (residential exposure), underground miners Lung
Bone Radium-224 and decay products Medical patients
Radium-226, radium-228, and decay products Radium-dial painters
Thorium-232 and decay products Medical patients
Plutonium Plutonium-production workers
Phosphorus-32 Medical patients
Fission products, includi ng strontium-90 General population, following nuclear reactor accident
Radioiodines, including iodine-131 Children and adolescents, following nuclear reactor accident
X-radiation or gamma-radiation Atomic-bomb suNivors, medical patients; in-utem exposure (offspring
of pregnant medical patients and of atomic-bomb suNivors)
Solar radiation General population
UV-emitting tanning devices General population
CUachronic lymphocytic leukaemia. BCCwbasaltell carcinoma. SCC squamouscell carcinoma.
Table: Radiation exposureswithsufficientevidence in humans
www.thelancet.com/oncology Vol tO August 2009
Bone, paranasal sinus and mastoid process (radium-226 only)
Liver, extrahepatic bile ducts, gall bladder, leukaemia (excluding Cll)
Lung, liver, bone
Acute leukaemia
Solid cancers, leukaemia
Thyroid
Salivary gland, oesophagus, stomach, colon, lung, bone, ski n (BCC),
female breast, urinary bladder, brain and CNS, leukaemia (excluding CU),
thyroid, kidney (atomic-bomb SUIVi vors, medical patients); multiple sites
(in-ute<o exposure)
Skin (BCC. SCC. melanoma)
Skin (melanoma), eye (melanoma, particularly choroid and ciliary body)
751
I News
Monograph Working Group
Members
B Armstrong-Co-Chair
(Australia), E (ardis-Co-Chair
(Spain); A Green (Australia);
D Krewski. R Mitchel. N Priest
(Canada); L Tomasek (Czech
Republic); K Baverstock (finland);
J-F Dore, J Hall, L Saba tier
(France); M Sokolnikov (Russian
federation); M Hill, M Little,
M Marshall, C Muirhead,
A Riddell (UK); D Brenner [unable
to attend). R Guilmette, D Hoel.
D Richardson, R Ullrich (USA)
of interest
NPworks for, and RM is a
consultant to. Atomic Energy of
Canada ltd. CM receives funding
from the UK Ministry of Defence.
JH receives funding from
Ele<tricite de France. AG receives
funding from l'Oreal Recherche.
752
Invited Specialists
None
Panel: Types of radiation classified in
Groupl
Ionising radiation
Alpha-particle emi tters
Beta-particle emi tters
X-rays and gamma-rays
Neutron radiation
Solar radiation
Ultraviolet radiation (wavelengths
lOG-400 nm, encompassing UVA,
UVB, and UVC)
ionisation and excitation events that
can produce a variety of molecular
lesions and clustered, complex DNA
damage
9
Subsequent processing of
this damage induces many responses
(eg, cell killing, chromosomal
aberrations, mutations, genomic
instability, cell transformation, and
bystander effects) that contribute
to carcinogenesis. Based on these
mechanistic considerations, all types
of ionising radiation were classified by
the Working Group as "carcinogenic to
humans" (Group 1).
Solar radiation is the main source of
human exposure to ultraviolet (UV)
radiation, which is further subdivided
into UVA, UVB, and UVC. The
ultraviolet component that reaches the
earth's surface comprises around 95%
UVA and 5% UVB; UVC is blocked by
stratospheric ozone. Epidemiological
studies have established a causal
association between exposure to solar
radiation and all major types of skin
cancer (table). The Working Group
reaffirmed the carcinogenicity of solar
radiation (Group 1).
Exposure to solar radiation causes
a specific mutation fingerprint
(cytidine to thymidine transition),
as a result of cyclobutane pyrimidine
dimers in DNA. This pattern had long
been att ri buted to UVB.'
0
However,
this same cytidine to thymidine
transition has been detected in
the ski n of UVA-treated mice" and
in the Tp53 gene of UVA-induced
or UVB-induced skin tumours in
hairless mice.
10
In humans, this
transition has been seen in TPS3 in
premalignant solar keratosis and in
malignant skin tumours.'' Based on
t hese mechanistic data, the Working
Group classified UV radiation as
"carcinogenic to humans" (Group 1).
The use of UV-emitting tanning
devices is widespread in many
developedcountries,especiallyamong
young women. A comprehensive
meta-analysis concluded that the risk
of cutaneous melanoma is increased
by 75% when use of tanning devices
starts before 30 years of age.
13
Additionally, several case-control
studies provide consistent evidence
of a positive association between
the use of UV-emitting tanning
devices and ocular melanoma."'
5
Therefore, the Working Group raised
the classification of the use of UV-
emitting tanning devices to Group 1,
"carcinogenic to humans".
While reviewing the studies of
occupational UV exposure, the
Working Group concluded that there
is "sufficient evidence" for ocular
melanoma in welders. '
6
'
7
However,
because welders are also exposed to
other harmful agents, this association
could not be attri buted specifically
to UV radiation. A full review of the
carcinogenic hazards of welding will
be undertaken by IARC with high
pri ority.
Fatiha El Ghissassi, Robert Baan, Kurt
Straif, Yann Grosse, Beatrice
Secretan, Wronique Bouvard, Lamia
Benbrahim-Tallaa, Nee/a Guha,
Crystal Freeman, Laurent Galichet,
Vincent Cogliano, on behalf of the
WHO International Agency for
Research on Cancer Monograph
Working Group
International Agency for Research on
Cancer, Lyon, France
The IARC authors declared no conflicts of i nterest.
Grosse Y, Baan R. Straif K, et al. A review of
human carcinogens-part A: pharmaceuticals.
Lancer Oncol2009; 10: 13-14.
UN Chernobyl Forum expert group "Health"
(EGH). Health effects of the Chernobyl
accident and special health care programmes.
Geneva; 2006. http://whqlibdocwho.int/publi
cations/2006/924l594179_eng.pdf.
3 Card is E, Howe G, Ron E, et al. Cancer
consequences of the Chernobyl accident:
20years on.) Radiol Prot 2006; 26: 127-40.
4 Darby S, Hill D. Auvinen A. et al. Radon in
homes and risk of lung cancer: collaborative
analysis of individual data from 13 European
case-control studies. BM) 2005; 330: 223.
National Research Council, Committee to
Assess Health Risks from Exposure to low
Levels of Ionizing Radiation, Board on
Radiation Effects, and Research Division on
Earth and Life Studies. Health effects of
exposure to radon; BEIRVI. Washington:
National Academies Press; 1999.
6 National Research Council, Committee to
Assess Health Risks from Exposure to l ow
Levels of Ionizing Radiation, Board on
Radiation Effects, and Research Division on
Earth and Life Studies. Health risks from
exposure to low levels of ionizi ng radiation:
BEIRVII, Phase 2. Washington: National
Academies Press; 2006.
7 Wakeford R, Li ttle MP. Ri sk coefficients for
childhood cancer after int rauteri ne i rradiation;
a review. fnt) Radial Biol 2003; 79: 293- 309.
8 Preston Dl . Cullings H, Suyama A, et al. Solid
cancer incidence i n atomic bomb survivors
exposed i n utero or as young children.
) Natl Cancer fnst 2008; 100: 428- 36.
9 Good head DT. Initial events i n the cellular
effects of ionizing radiations: clustered
damage i n DNA. fnt) Radiat Biol1994;
65:7-17.
10 Rungcr TM, Kappes UP. Mechanisms of
mutation formation with long-wave
ultraviolet light (UVA). Photodermatol
Photoimmunol Photomed 2008; 24: 2-10.
11 lkehata H, Kawai K, Komuraj, etal. UVA1
genotoxicity is mediated not by oxidative
damage but by cyclobutane pyrimidine dimers
i n normal mouse ski n.) Invest Dermotol2008;
128: 2289-96.
12 Agar NS, Hall iday GM, Barnetson RS,
Ananthaswamy HN, Wheeler M, jones AM.
The basal layer in human squamous tumors
harbors more UVA than UVB fingerpri nt
mutations: a role for UVA i n human skin
carci nogenesis. Proc Natl Acod Sci USA 2004;
101: 4954-59
13 !ARC Working Group. The association of use of
sunbeds with cutaneous malignant melanoma
and other skin cancers: a systematic review.
lnt) Cancer 2006; 120: 1116-22.
14 Seddon JM, Gragoudas ES. Glynn Rj , Egan KM,
Albert DM, Blitzer PH. Host factors, UV
radiation, and risk of uveal melanoma: a
casecontrol study. Arch Ophthalmol1990;
108: 1274-80.
15 Vajdic CM, Kri cker A, Giblin M, et al. Artificial
ultraviolet radiation and ocular melanoma in
Australia. In!) Cancer 2004; 112: 896-900.
16 Lutz )M, Cree I, Sabroe S, et al. Occupational
risks for uveal melanoma results from a case
control study in nine European countries.
CancerCausesControi200S; 16:437-47.
17 Shah CP, WeisE. Lajous M. Shields )A.
Shields CL. Intermittent and chronic ultraviolet
light exposure and uveal melanoma: a meta-
analysis. Ophthalmology 2005; 112: 1599-607.
www.t helancet.com/oncology Vol10 August 2009
News I
Special Report: Policy
A review of human carcinogens-Part D: radiation
In June 2009, 20 scientists from nine
countries met at the International
Agency for Research on Cancer (IARC)
to reassess the carcinogenicity of the
types of radiation previously classified
as "carcinogenic to humans" (Group 1)
and to ident ify additional tumour sites
and mechani sms of carcinogenesis
(table and panel). These assessments
wil l be published as part D of Volume
100 ofthe I ARC Monographs.'
Alpha particles, consisting of two
protons and two neutrons, are a
densely ionising type of radiat ion
wi th low capaci ty to penet rate living
tissue (less than 0-1 mm). Beta
particles are electrons or positrons
that are less ionising, but more
penetrating (up to a few milimetres).
The health hazards resulting from
radionuclides that emit these
particles largely occur after internal
deposition. Epidemiological evidence
shows a number of radionuclides that
emit alpha or beta particles increase
cancer risks at several anatomical sites
(table). The Worki ng Group reaffirmed
the carcinogenicity of internally
deposited radionuclides that emit
alpha or beta particles (Group 1).
Radiation type
Alpha-particle and beta-particle emitters
After the Chernobyl accident. a
sharp increase in the risk of thyroid
cancer was found with exposure to
radioiodines, particularly iodine-131,
during chi ldhood and adolescence.u
This increased risk might be due to
higher milk intake per unit of body
weight among chi ldren; a higher thyroid
dose per unit of iodine-131 intake from
milk; a higher susceptibility per unit of
thyroid dose; or a combination of these.
Radon exposure occurs mainly
through contamination of indoor
air by radon released from soil and
building materials. Combined analyses
of case-control studies now estimate
that residential exposure to radon gas
is the leading cause of lung cancer after
tobacco smoke (8-15% attributable
risk in Europe and North America).-
5
X-rays and gamma-rays are
sparsely ion1smg electromagnetic
radiation that penetrate living tissue,
typical ly producing fast electrons that
deposit energy, resulting in tissue
damage. Extensive study of atomic-
bomb survivors shows increased
cancer risks at multiple anatomical
sites.
6
Current evidence adds to the
list of tumours caused by x-rays
Major study populations
and gamma-rays (table), and also
establishes that in-utero exposure
increases the risk of cancer at multiple
sites.
7

8
The Working Group reaffirmed
the carcinogenicity of x-radiation and
gamma-radiation (Group 1).
Neutrons are produced by nucl ear
reactions and are a main component
of cosmic radiation. They are highly
penetrating and interact with
the t raversed tissue, producing
protons, other charged part icles, and
gamma-radiation. Epidemiological
evidence is inadequate to assess the
carcinogenicity of neutrons, because
of co-exposures to other types of
radiation. However, the evidence
of cancer in experimental animals
is sufficient, and mechanistic data
show that neutrons t ransfer their
energy in clusters of ionising events-
resulting in similar, but more severe,
local damage than that induced by
x-rays or gamma-rays. On the basis
of this evidence, the Working Group
reaffirmed the carcinogenicity of
neutron radiation (Group 1).
Each type of ionising radiation
(panel) transfers energy in the
form of highly structured tracks of
Upcoming meetings
Sept 29-0ct 6, 2009
Lifestyle Factors
Oct 20-27, 2009
Chemical Agents and Related
Occupations
http://monographs.iarc.fr/
Tumour sites (and types) on which sufficient evidence is based
Radon-222 and decay products General population (residential exposure), underground miners Lung
Bone Radium-224 and decay products Medical patients
Radium-226, radium-228, and decay products Radium-dial painters
Thorium-232 and decay products Medical patients
Plutonium Plutonium-production workers
Phosphorus-32 Medical patients
Fission products, includi ng strontium-90 General population, following nuclear reactor accident
Radioiodines, including iodine-131 Children and adolescents, following nuclear reactor accident
X-radiation or gamma-radiation Atomic-bomb suNivors, medical patients; in-utem exposure (offspring
of pregnant medical patients and of atomic-bomb suNivors)
Solar radiation General population
UV-emitting tanning devices General population
CUachronic lymphocytic leukaemia. BCCwbasaltell carcinoma. SCC squamouscell carcinoma.
Table: Radiation exposureswithsufficientevidence in humans
www.thelancet.com/oncology Vol tO August 2009
Bone, paranasal sinus and mastoid process (radium-226 only)
Liver, extrahepatic bile ducts, gall bladder, leukaemia (excluding Cll)
Lung, liver, bone
Acute leukaemia
Solid cancers, leukaemia
Thyroid
Salivary gland, oesophagus, stomach, colon, lung, bone, ski n (BCC),
female breast, urinary bladder, brain and CNS, leukaemia (excluding CU),
thyroid, kidney (atomic-bomb SUIVi vors, medical patients); multiple sites
(in-ute<o exposure)
Skin (BCC. SCC. melanoma)
Skin (melanoma), eye (melanoma, particularly choroid and ciliary body)
751
I News
Monograph Working Group
Members
B Armstrong-Co-Chair
(Australia), E (ardis-Co-Chair
(Spain); A Green (Australia);
D Krewski. R Mitchel. N Priest
(Canada); L Tomasek (Czech
Republic); K Baverstock (finland);
J-F Dore, J Hall, L Saba tier
(France); M Sokolnikov (Russian
federation); M Hill, M Little,
M Marshall, C Muirhead,
A Riddell (UK); D Brenner [unable
to attend). R Guilmette, D Hoel.
D Richardson, R Ullrich (USA)
of interest
NPworks for, and RM is a
consultant to. Atomic Energy of
Canada ltd. CM receives funding
from the UK Ministry of Defence.
JH receives funding from
Ele<tricite de France. AG receives
funding from l'Oreal Recherche.
752
Invited Specialists
None
Panel: Types of radiation classified in
Groupl
Ionising radiation
Alpha-particle emi tters
Beta-particle emi tters
X-rays and gamma-rays
Neutron radiation
Solar radiation
Ultraviolet radiation (wavelengths
lOG-400 nm, encompassing UVA,
UVB, and UVC)
ionisation and excitation events that
can produce a variety of molecular
lesions and clustered, complex DNA
damage
9
Subsequent processing of
this damage induces many responses
(eg, cell killing, chromosomal
aberrations, mutations, genomic
instability, cell transformation, and
bystander effects) that contribute
to carcinogenesis. Based on these
mechanistic considerations, all types
of ionising radiation were classified by
the Working Group as "carcinogenic to
humans" (Group 1).
Solar radiation is the main source of
human exposure to ultraviolet (UV)
radiation, which is further subdivided
into UVA, UVB, and UVC. The
ultraviolet component that reaches the
earth's surface comprises around 95%
UVA and 5% UVB; UVC is blocked by
stratospheric ozone. Epidemiological
studies have established a causal
association between exposure to solar
radiation and all major types of skin
cancer (table). The Working Group
reaffirmed the carcinogenicity of solar
radiation (Group 1).
Exposure to solar radiation causes
a specific mutation fingerprint
(cytidine to thymidine transition),
as a result of cyclobutane pyrimidine
dimers in DNA. This pattern had long
been att ri buted to UVB.'
0
However,
this same cytidine to thymidine
transition has been detected in
the ski n of UVA-treated mice" and
in the Tp53 gene of UVA-induced
or UVB-induced skin tumours in
hairless mice.
10
In humans, this
transition has been seen in TPS3 in
premalignant solar keratosis and in
malignant skin tumours.'' Based on
t hese mechanistic data, the Working
Group classified UV radiation as
"carcinogenic to humans" (Group 1).
The use of UV-emitting tanning
devices is widespread in many
developedcountries,especiallyamong
young women. A comprehensive
meta-analysis concluded that the risk
of cutaneous melanoma is increased
by 75% when use of tanning devices
starts before 30 years of age.
13
Additionally, several case-control
studies provide consistent evidence
of a positive association between
the use of UV-emitting tanning
devices and ocular melanoma."'
5
Therefore, the Working Group raised
the classification of the use of UV-
emitting tanning devices to Group 1,
"carcinogenic to humans".
While reviewing the studies of
occupational UV exposure, the
Working Group concluded that there
is "sufficient evidence" for ocular
melanoma in welders. '
6
'
7
However,
because welders are also exposed to
other harmful agents, this association
could not be attri buted specifically
to UV radiation. A full review of the
carcinogenic hazards of welding will
be undertaken by IARC with high
pri ority.
Fatiha El Ghissassi, Robert Baan, Kurt
Straif, Yann Grosse, Beatrice
Secretan, Wronique Bouvard, Lamia
Benbrahim-Tallaa, Nee/a Guha,
Crystal Freeman, Laurent Galichet,
Vincent Cogliano, on behalf of the
WHO International Agency for
Research on Cancer Monograph
Working Group
International Agency for Research on
Cancer, Lyon, France
The IARC authors declared no conflicts of i nterest.
Grosse Y, Baan R. Straif K, et al. A review of
human carcinogens-part A: pharmaceuticals.
Lancer Oncol2009; 10: 13-14.
UN Chernobyl Forum expert group "Health"
(EGH). Health effects of the Chernobyl
accident and special health care programmes.
Geneva; 2006. http://whqlibdocwho.int/publi
cations/2006/924l594179_eng.pdf.
3 Card is E, Howe G, Ron E, et al. Cancer
consequences of the Chernobyl accident:
20years on.) Radiol Prot 2006; 26: 127-40.
4 Darby S, Hill D. Auvinen A. et al. Radon in
homes and risk of lung cancer: collaborative
analysis of individual data from 13 European
case-control studies. BM) 2005; 330: 223.
National Research Council, Committee to
Assess Health Risks from Exposure to low
Levels of Ionizing Radiation, Board on
Radiation Effects, and Research Division on
Earth and Life Studies. Health effects of
exposure to radon; BEIRVI. Washington:
National Academies Press; 1999.
6 National Research Council, Committee to
Assess Health Risks from Exposure to l ow
Levels of Ionizing Radiation, Board on
Radiation Effects, and Research Division on
Earth and Life Studies. Health risks from
exposure to low levels of ionizi ng radiation:
BEIRVII, Phase 2. Washington: National
Academies Press; 2006.
7 Wakeford R, Li ttle MP. Ri sk coefficients for
childhood cancer after int rauteri ne i rradiation;
a review. fnt) Radial Biol 2003; 79: 293- 309.
8 Preston Dl . Cullings H, Suyama A, et al. Solid
cancer incidence i n atomic bomb survivors
exposed i n utero or as young children.
) Natl Cancer fnst 2008; 100: 428- 36.
9 Good head DT. Initial events i n the cellular
effects of ionizing radiations: clustered
damage i n DNA. fnt) Radiat Biol1994;
65:7-17.
10 Rungcr TM, Kappes UP. Mechanisms of
mutation formation with long-wave
ultraviolet light (UVA). Photodermatol
Photoimmunol Photomed 2008; 24: 2-10.
11 lkehata H, Kawai K, Komuraj, etal. UVA1
genotoxicity is mediated not by oxidative
damage but by cyclobutane pyrimidine dimers
i n normal mouse ski n.) Invest Dermotol2008;
128: 2289-96.
12 Agar NS, Hall iday GM, Barnetson RS,
Ananthaswamy HN, Wheeler M, jones AM.
The basal layer in human squamous tumors
harbors more UVA than UVB fingerpri nt
mutations: a role for UVA i n human skin
carci nogenesis. Proc Natl Acod Sci USA 2004;
101: 4954-59
13 !ARC Working Group. The association of use of
sunbeds with cutaneous malignant melanoma
and other skin cancers: a systematic review.
lnt) Cancer 2006; 120: 1116-22.
14 Seddon JM, Gragoudas ES. Glynn Rj , Egan KM,
Albert DM, Blitzer PH. Host factors, UV
radiation, and risk of uveal melanoma: a
casecontrol study. Arch Ophthalmol1990;
108: 1274-80.
15 Vajdic CM, Kri cker A, Giblin M, et al. Artificial
ultraviolet radiation and ocular melanoma in
Australia. In!) Cancer 2004; 112: 896-900.
16 Lutz )M, Cree I, Sabroe S, et al. Occupational
risks for uveal melanoma results from a case
control study in nine European countries.
CancerCausesControi200S; 16:437-47.
17 Shah CP, WeisE. Lajous M. Shields )A.
Shields CL. Intermittent and chronic ultraviolet
light exposure and uveal melanoma: a meta-
analysis. Ophthalmology 2005; 112: 1599-607.
www.t helancet.com/oncology Vol10 August 2009
Press Release N 171 Page 1 of 3
International Agency for Research on Cancer
PRESS RELEASE
N171
WHO 29 Novembre 2006
Sunbed use in youth unequivocally associated with skin cancer
In October 2004, the French Mini stry of Healt h contacted Dr Peter Boyle, the Director of the
rai sing a particular concern about the increase in incidence of melanoma ir
Fr ance and in the world. Melanoma is the most deadly form of skin cancer. For reference, while
Europe registers 10- 15 cases per 100,000 population and per year, Australia has an incidence
of 50 cases/100,000 population ever y year. Melanoma is on the increase everywhere in the
world and the number of cases doubl es every 12-15 years in the most affected areas.
In 1992, an IARC Working Gr oup made a thorough review of the available scientific data anc
concluded that solar radiation is carcinogenic to humans (Group 1)(2). Solar radiat ion
cutaneous melanoma and non-mel anoma skin cancer. However, there is stil l
surrounding the role of exposure to artificial sources of UV radiation, i.e. from the use ol
sunbeds or sunlamps in t anning parlours, in t he aet iology of skin cancer.
IARC Review of the literature
To respond to these concerns, IARC convened an international Working GroupC
3
) that assessee
the availabl e evidence relating to health effects, both positive and detrimental, of exposure tc
arti f icial UV r adiation through t he use of indoor tanning facilities, in particular whether thei1
use increases t he ri sk for skin cancer.
Assessment
Epidemiologic studies do not provide consistent evidence that use of indoor tanning faci lities ir
general is associated with the development of melanoma or non- melanoma skin cancer<
4
).
There are various technical explanations for this conclusion. Firstly, knowledge of levels of U'v
exposure during indoor t anning is ver y imprecise. Furthermore, early studies published had lo'll
power to detect long-term associations with artif icial UV exposure that become evident
following a prolonged lag period. "Consideri ng simultaneously all the avai lable data", Dr Boyle
said, "made it possible for us to reach a number of clear conclusions."
Conclusions
1. Clear increase in melanoma risk associated with use of sun beds in teens and twenties
The data showed a prominent and consist ent increase in risk for melanoma in people who firs1
used sunbeds in t heir t wenti es or t een year s: a 75% increase in risk of melanoma
calculated for such users of artificial tanning appliances, whi le this increase in the genera
population, although not statistically significant, is still not negligible.
2. Increase in risk of squamous cell cancer (SCC) of the skin associated with use of sunbeds ir
teens
Li mited data suggest that the ri sk of squamous cell carcinoma is similarly increased after f i rs1
use as a teenager.
3. Immune system affected
http://www .iarc.fr/ENG/Press_Releases/pr 171 a.html 4/17/2008
Press Release N 171 Page 2 of3
Data also suggest detrimental effects from use of sunbeds on the skin's immune response and
possibly on the eyes (ocular melanoma).
4. No positive health effects
Artificial tanning confers little if any protection against solar damage to the skin, nor does use
of indoor tanning facil ities grant protection against vitamin D deficiency. Data also suggest
detrimental effects from use of indoor tanning facilities on the skin's immune response and
possibly on the eyes (ocular melanoma).
Public Health message
Dr Boyle concluded that "while !ARC's mandate is one of scientific expertise and assessment of
epidemiologic risk, in view of the strength and seriousness of the findings, effective action to
restrict access to artificial tanning facilities (solariums, tanning salons, tanning parlours) to
minors and young adults should be strongly considered."
Notes:
(1) The International Agency for Research on Cancer (IARC) is part of the World Health
Organization. Its mission is to coordinate and conduct research on the causes of human
cancer, the mechanisms of carcinogenesis, and to develop scientific strategies for cancer
control. The mandate of the world cancer research agency is to coordinate international
research to take advantage of synergies and disseminate scientific information through
publications, meetings, courses, and fellowships.
(2) UV radiations A, B and C were all three independently rated as probably carcinogenic to
humans by the IARC Working Group in 1992. In addition, they concluded that the "use of
sunlamps and sunbeds entails exposures that are probably carcinogenic to humans (Group
2A)" . While natural UV radiation does indeed stimulate the production of indispensable vitamin
D, exposure to natural sun light should be moderate, and in any case artificial UV radiation
exposure, as provided by sunbed exposure, should be avoided at all cost.
(3) The members of the Working Group were: Dr Philippe Autier
1
, Dr Mathieu Boniol
1
, Dr Peter
Boyle
1
, Dr Jean-Francais Dore
2
, Dr Sara Gandini
3
, Dr Adele Green (Chair)
4
, Dr Julia Newton-
Bishop5, Dr Martin A. Weinstock
6
, Dr Johan Westerdah1
7
, Dr Beatrice Secretan (Coordinator)
1
,
Dr Stephen Walter
8
. Their conclusions are being published online by the I nternatlonaLJo_urnal
of Cancer
1
IARC -
2
INSERM U590, Centre Leon Berard, Lyon, France -
3
European Institute of Oncology,
Milan, Italy -
4
Queensland Institute of Medical Research, Australia -
5
Cancer Research UK -
6
Brown University Medical School - USA -
7
Lund University Hospital - Sweden [unable to
attend] -
8
McMaster University - Ontario, Canada
( 4) There are three main types of cancers of the skin: Basal cell carcinoma (BCC) is the
most common form of cancer and the least aggressive. Basal cells are cells that line the
deepest layer of the epidermis. A tumor of this layer is known as basal cell carcinoma. The sun
is responsible for over 90 percent of all skin cancers, including BCC, and chronic overexposure
to sunlight is the cause for most cases of basal cell carcinoma. BCCs occur most frequently on
the face, ears, neck, scalp, shoulders, and back. Squamous cell cancer (SCC) is a malignant
tumor. It is more aggressive than basal cell cancer, and is more likely than basal cell cancer to
metastasize. Melanoma is the most dangerous type of skin cancer. It involves the cells that
produce pigment (melanin), which is responsible for skin and hair color. The development of
melanoma is related to sun exposure, particularly to sunburns during childhood, and is most
common among people with fair skin, blue or green eyes, and red or blond hair.
http://www .iarc.fr/ENG/Press_Releases/pr 171 a.html 4/17/2008
Press Release N 171
World Health Organization
International Agency for Research on Cancer
Page 3 of3
Organisation mondiale de Ia Sante
Centre international de Recherche sur le Cancer
150, cours Albert-Thomas 69372 lyon Cedex 08 (France)
Telephone: 33 472 738 485 Facsimile: 33 472 738 311 http:/ /www.iarc.fr
http://www .iarc.fr/ENG/Press_Releases/pr 171 a.html 4/17/2008
----------ICNIRP Statement ----------
HEALTH ISSUES OF ULTRA VIOLET TANNING APPLIANCES
USED FOR COSMETIC PURPOSES
-----------ICNIRP Statement-----------
HEALTH ISSUES OF ULTRAVIOLET TANNING APPLIANCES
USED FOR COSMETIC PURPOSES
The International Commission on Non-Ionizing Radiation Protection*
BACKGROUND
Consumer demand for a cosmetic tan is the eco-
nomic basis of the "suntanning industry," which devel-
ops and distributes equipment for commercial suntanning
and markets suntanning services to consumers.
Suntanning is caused by ultraviolet radiation
(UVR).t Exposure from sunbeds and other tanning ap-
pliances has the same potential risks as exposure to the
UVR in solar radiation. The term "sunbed" is frequently
used to describe all tanning appliances consisting of
either a single UVR-emitting lamp (emitting UV A and/or
UVB radiation) as in some facial tanners or a number of
such lamps incorporated into a bed, canopy, panel, or any
combination thereof.
Potential adverse health effects of exposure to UVR
are well documented and reasonably well quantified
(WHO 1994). The purpose of this document is to
summarize the potential adverse effects of exposure to
ultraviolet radiation from tanning appliances and to
provide recommendations to minimize the risks of such
effects. Recommendations in this document apply o ly to
the use of sunbeds for cosmetic purposes.
TANNING APPLIANCES: TYPES AND
EMISSION CHARACTERISTICS
There are two distinctly different categories of
ultraviolet appliances used in tanning applications, each
with different UVR emission characteristics and different
requirements for filtering to eliminate undesirable wave-
lengths:
* ICNIRP c/o BfS, Institut fur Strahlenhygiene, Ingolstaedter
Landstr. L 85764 Oberscbleissheim, Gennany.
For correspondence or reprints contact: R. Matthes at the above
address, or email at r.matthes@icnirp.org.
t The International Commission on Illumination (CIE) defines
UVR as optical radiation between I 00 and 400 nm, and this spectral
region is divided into three photobiological spectral regions: UVC
(100-280 nm), UVB (280-315 nm) and UVA (315-400 nm).
(Manuscript received 1 May 2002; accepted 23 July 2002)
0017-9078/03/0
Copyright 2003 Health Physics Society
119
Low-pressure fluorescent tubes, emitting mostly UV A
or mostly UVB, with broad-band or narrowband emis-
sion; and
Filtered high pressure and high intensity discharge
lamps, emitting virtually only UV A or a mixture of
UVA and UVB.
Tanning appliances are currently the subject of an
international standard established by the International
Electrotechnical Commission (IEC 1995), which has
regulatory status in some countries. Four types of appli-
ances are recognized in this standard and defined by this
standard as follows:
UV type 1 appliances are those that emit UV radiation
such that the biological effect is caused by radiation
having wavelengths longer than 320 run and charac-
terized by a relatively high irradiance (;?; 0.15 W m-
2
)'
in the range 320 nm to 400 nm. The emission at
wavelengths less than 320 run is limited to 0.5 mW
-2
m,
UV type 2 appliances are those that emit UV radiation
such that the biological effect is caused by radiation
having wavelengths both shorter and longer than 320
run and characteiized by a relatively high irradiance
(;?; 0.15 W m-
2
;) in the range 320 run to 400 nm. The
it-radiance at wavelengths less than 320 run is in the
range 0.5-150 mwm-
2
;
UV type 3 appliances are those that emit UV radiation
such that the biological effect is caused by radiation
having wavelengths both shorter and longer than 320
nm and characterized by a limited it-radiance ( :5 0.15
W m
2
) in each UV radiation band; and
UV type 4 appliances are those that emit UV radiation
such that the biological effect is mainly caused by
radiation having wavelengths shorter than 320 nm (at
an irradiance greater than 0.15 W m
2
, and in the
wavelength range 320-400 nm, the it-radiance is
limited to 0.15 W m
2
).
*All it-radiances are erythemally weighted. In their international
standard, the International Electrotechnical Commission (IEC), has
used the wave length ranges from 320-400 nm and <320 nm to
characterize the UV radiation.
120 Health Physics
The emission characteristics and the health risks
associated with the use of each type of appliance are
different (Gies et al. 1986). Type 4 appliances, associated
with high levels of emission of UVB (280-3 15 nm), are
intended to be used following medical advice and should
not be used for tanning purposes, mainly because of the
publicized association between UVB and skin cancer.
Most of the appliances that are in use today are UY A-
emitting (315-400 nm) appliances, UV types I, 2, and 3.
The term "sun beds" in this document refers to UV-
emitting appliances of UY type 1, 2, and 3, although UV
type 4 appliances are still marketed to commercial
suntanning establishments.
During the last decade, increasing evidence of long
term UV A-induced risks for the skin and the eye has led
the sun-tanning industry to increase the UVB content in
the emission spectrum of tanning lamps in order to more
closely simulate natural sun exposure. This change has
also permitted shorter tanning exposures. It is known that
the ratio of UV A to U VB in the solar spectrum changes
during the day and undergoes large variations according
to season and latitude. It is also important to recognize
that there is no firm scientific evidence to indicate that
tanning with either UVA-dominated or a UVB-
dominated sources poses less risk; and, likewise, the use
of a simulated solar spectrum is not necessarily "safer"
than other artificial sources.
EFFECTS ON SKIN
Tanning
When skin .is exposed to UVR, two distinct tanning
reactions ensue:
Immediate pigment darkening (IPD). IPD begins
immediately on exposure to UVR and is caused by the
darkening of the pigment melanin that is already present
in the skin; it is n01mally seen only in people who have
at least a moderate constitutive tan. Such pigmentation
begins to fade within a few minutes after cessation of
exposure. Radiation between 320 and 400 nm is regarded
as being most effective for IPD (Irwin et al. 1993).
January 2003, Volume 84. Number I
Delayed tanning (neo-melanogenesis). The visible
pigmentation takes at least 3 d to develop and results
from exposure to U VA but is more effectively produced
by UVB (Parrish et al. 1982; Gange et al. 1985).
UVR-induced neo-melanogenesis is strongly dependent
on cellular responses arising from UVR-induced DNA
damage in cellular nuclei (Eller et al. 1996; Gilchrest et
al. 1996). Delayed tanning is more persistent than IPD
and results from an increase in the number, size, and
pigmentation of melanin granules (Bech-Thomsen et al.
1994). Exposure to UVB results also in an increase in the
thickness and scattering properties of the epidermis
(outer layer of the skin) (Bech-Thomsen and Wulf 1995).
Due, at least in part, to these processes, the tan obtained
from a pure UV A appliance, while perhaps cosmetically
acceptable, is not as effecti ve in protecting against
further exposure to solar UYR as the equivalent pigmen-
tation induced by exposure to solar radiation.
The degree to which an individual successfully tans
as the result of exposure on a sunbed depends critically
on his/her skin phototype as judged by his/her ability to
tan and the susceptibility to sunburn as a result of
exposure to solar UVR. Different skin phototypes (clas-
sified as phototypes I through VI) are presented in Table
l. In principle, the reaction of a person to UVR with
respect to tanning or sunburning is similar whether the
exposure is on a sunbed or to solar radiation.
Among users of artificial suntanning devices, persons
of skin phototypes I and II, who do not tan well and/or who
sunbum easily, are likely to be disappointed with the
cosmetic results of using a sunbed. It has also been
recognized that many users experience minor adverse cuta-
neous effects such as mild erythema, itching, and skin
dryness (Diffey 1986; Rivers et al. 1989; Diffey et al. 1990).
Individual users of tanning appliances and attendants at
tanning salons may incorrectly evaluate individual skin
sensitivity to UVR and underestimate the user's sensitivity.
Sunburn
Minor sunburn is a skin reddening (actinic ery-
thema) that appears up to 12 h after UVR exposure.
Table 1. Classification of skin phototypes based 011 their susceptibility to sunburn in sunlight and their ability to tan
(Fitzpatrick et al. 1995).
Skin
phototype Sun sensitivity Sunburn susceptibility" Tanning ability Classes of individuals
I Very sensitive Always sunburn ( <2 SED) No tan Melano-compromizedb
IT Moderately sensitive High (2-3 SED) Light tan Melano-compromizedb
rn Moderately insensiti ve Moderate (3-5 SED) Medi.um tan Melano-competent
IV Moderately resistant Low (5-7 SED) Dark tan Melano-competent
v Resistant Very low (7- 10 SED) Natural brown skin Melano-protected
VI Very resistant Extremely low (> I 0 SED) Natural black skin Melano-protected
1 Tbe ranges of SEDs in parentheses are only indicative.
b Melano-compromized individuals have a greater risk of developing skin cancers than melano-competent individuals.
Health issues of ultraviolet tanning appliances e ICNTRP 121
Erythema gradually fades after a few days, replaced by
some tanning in individuals with tanning capability.
Severe sunburn is painful and results in inflammation,
blistering, and peeling of the skin. Aside from photoim-
munological effects (discussed later), systemic effects of
severe sunbum are unknown except for transient fever.
Sunburn severity depends Ciitically on skin phototype
(Table I) and UV dose. For fair-skinned people (skin
phototypes I and II, melano-compromised), the relative
effectiveness of UVR for tanning and for erythema is
approximately the same over the entire range of UVB
and UV A wavelengths (PaiTish et al. 1982). For people
who tan well and who rarely sunburn (skin phototypes ill
and IV, melano-competent), the tanning efficacy of UVA
is higher than its erythemal efficacy (Gange et a!. 1985).
For a given sunbed type, there is a range of radiant
exposures which can be expressed in terms of Standard
Erythemal Dose (SED) unit related to the Minimal
Erythemal Doses (MEDs), that will produce noticeable
effects in people of different skin pbototypes.
Skin cancer
The most serious long-term effects attributed to
UVR exposure of the skin are the skin cancers (!ARC
1992). Squamous and basal cell carcinomas are common,
rarely fatal forms of skin cancer, which are often referred
to collectively as non-melanoma skin cancers (NMSCs).
Experimental studies clearly indicate that UV A and UVB
can cause squamous cell carcinomas (SCCs) in mice. The
same effects are likely in humans (Sterenborg 1987; van
Weelden et al. 1988). The erythemal potential of a UVR
source is gaining acceptance as a reasonable approxima-
tion for a quantitative measure of its carcinogenic poten-
tial (Cole et al. 1985). A series of publications (Berget
al. 1993; de Gruijl et al. 1993; de Gruijl and van der Leun
1994; de Gruijl and Forbes 1995) has been a source for
the proposal of an action spectrum for photocarcinogen-
esis by CIE TC 6-32 (CIE 2000). It will be used to
evaluate the maximal number of authorized yearly ses-
sions as the basis of a recommendation in the next
revision of the international standard, IEC 335-2-27.
Efforts to estimate the increased 1isk of a series of
tanning sessions have been made; however, these have
A minimum erythemal dose (MED) is defined as the UVR
exposure that will produce a "just noticeable" erythema on previously
unexposed skin of an individual. If the exposure is spectrally weighted
by the CIE erythemal action spectrum, the l\IIED corresponds to an
effective radiant exposwe expressed in Standard Erythemal Dose (SED)
units, depending on individual skin phototype (Table I). Erythemally
effective it-radiances (W m
2
eff.), expressed in SEDs per hour, can be
calculated for any source of UVR using spectral k-radiance data for tbe
source, at the poi.nt of interest, and the relative spectral weighti11g factors
for erythema, promulgated by the CIE (McKinlay and Di ffey 1987;
CIE/ISO 1999). One SED (Diffey et al. 1997) is a CIE/ISO official unit,
and effective radiant exposure of 100 J m
1
.
been limited to non-melanoma skin cancer, and such
estimates necessarily require a number of assumptions
such as the dose-response function, the use of ecological
rather than individual-based data to estimate the relation
between UV exposure and risk, the extent of natural
exposure, and neglecting its intermittency. For example,
estimates of the tisk of incidence of NMSC due to the use
of UV A sunbeds suggest a doubling of risk for no more
than 20 sessions per year over 30 y in Northern Europe
population (Diffey 1987). Despite these health risks, if
individuals insist on acquiring a tan, there are conclu-
sions that can be drawn from the scientific data to
minimize risk such as presented in the recommendation.
Based upon a modeling of human skin-cancer risk
(Diffey 1987), 10 sessions of 30 min per year will
increase by 5% the risk of skin cancer compared with
non-users of solaria. A "safe" level of solarium use does
not exist.
Cutaneous malignant melanoma (MM), while much
less hequent than NMSC, is much more serious and
accounts for the majotity of deaths from skin cancer.
There are some mammalian data (Ley et al. 1989; Ley
1997) for MM that indicate a strong UVB melanoma
etiology, but these data are not entirely consistent with
data from a fish melanoma model that indicate a strong
implication of UV A in addition to UVB in the induction
of fish melanoma (Setlow 1993). The animal models
demonstrate an increased impact of neonatal exposure on
tumor induction including malignancy (Robinson et al.
2000; Noonan et al. 2001). The evidence for the indict-
ment of sunlight as a causal agent is limited to epidemi-
ological data. The data indicate that intermittent exposure
to high levels of solar UVR, particularly at an early age,
may be a contributing causal factor (for recent review see
Armstrong and Kricker 1995; Gilchrest eta!. 1999). The
individual risk of MM is higher in people who have a
large number of nevi (moles) and who sunburn readily
and tan poorly with exposure to solar UVR. Some data
suggesting an association between the use of sunbeds and
an increased risk of MM have been published, but it is
unclear as to the relative importance of UVB, UVA, and
other factors (especially, general sun-seeking behavior)
in causing this association (Swerdlow et al. 1988; Walter
et al. 1990; Au tier et al. 199 l ; Higgins and du Vivier
1992; Westerdahl et al. 1994; Autier et al. 1994; Spencer
and Amonette 1995; Stem et al. 1997; Miller et al. 1998;
Swerdlow and Weinstock 1998; Westerdahl et al. 2000).
Taken collectively, both experimental and epidemi-
ological data on skin cancer all indicate that cumulative
exposure increases the risk for skin cancers. This in-
cludes childhood exposures. Therefore, the added expo-
sure from UV tanning appliances is likely to add to the
detrimental consequences of natural solar exposure.
122 Health Physics
Premature skin aging
There is considerable evidence that cumulative
UVR (UV A and UVB) exposure results in premature
skin aging characterized by a dry, coarse, leathery, and
wrinkled appearance. It bas been clearly demonstrated
that UV A causes skin damage in mice (Kligman et al.
1987; Bissett et al. 1989). Similar effects might be
expected in humans as a result of excessive use of
sun beds.
Daily exposures to suberythemogenic purely UVA
within the spectral region 320-400 nm for 8 d or
exposure to longer UV A wavelengths between 340-400
nm for 2 mo result in cumulative morphological skin
alterations, which are indicative of tissue injury (Lavker
et al. 1995; Lowe et al. 1995; Seite et al. 1998). In a
5-year longitudinal study of women who used or did not
use tanning salons (Pierard 1998), serious modifications
of skin elasticity and extensibility were found in the
tanning salon user group. In that group, the severity of
skin disorders was inversely correlated with their natural
pigment capacities. It has been concluded from the study
that the unremitting use of sunbeds induces a functional
decline of the dermis resembling premature aging.
Table 2. Agents producing photosensitivity.
Agents Incidence
January 2003, Volume 84, Number 1
Other skin effects
People who have excessively used UV A sunbeds have
exhibited increased skin fragility and blistering (Parr- et al.
1988; Murphy et al. 1989) and atypical melanocytic lesions
(Jones et al. 1987; Williams et al. 1988; Roth et al. 1989;
Salisbury et al. 1989; Kadunce et al. 1990).
Photodermatosis and photosensitivity
Polymorphic light eruption (PLE) is a common
photodennatosis readily produced in some people by
exposure to UV sunbed radiation (Rivers et al. 1989).
Other photoaggravated dermatoses such as systemic
lupus erythematosus are also exacerbated by the use of
UV sunbeds (Stern and Docken 1986). Certain medicines
and chemical and topical products (Table 2) such as
perfumes and lotions may cause skin photosensitization
in sunbed users.
PHOTOIMMUNOLOGICAL EFFECTS
UVR exposure causes localized skin and systemic
modifications due to photoimmuno1ogical reactions
(Noonan and De Fabo 1990), also a particular concern
with UV A sunbed radiation (Hersey et al. 1988; Rivers et
Type of reaction
Effective
wavelength
range
Agents producing photosensitivity at local administration
Sulphonamides and rela1ed chemicals n.a.a phototoxic and
(sunscreens. blancophores) photoallcrgic
Disinfeclw11s (salicylanilide compounds n.a. phototoxic and
in soaps and deodorants) photoattergic
Phenothiazines (creams, dyes and n.a. pbot.otoxic and
insecticides) photoallergic
Dyes n.a. phototoxic
hypetpigmcntation
Coal tar and derivalives (phenolic n.a. phototoxic
compounds)
Essential oils (perfumes and colognes) n.a. phototoxic
hyperpigmentation
Furocoumarines compounds (psoratens) n.a. phot.otoxic
hyperpigmentation
Cadmium sulphide (tanoos) o.a. phototoxic
Agents producing pbot.oseositivity after oral or parenteral administration
Amiodarone
Thiazide diuretics
Chlorpromazine and related
phmo1hiazines
Nalidixic acid
Non sleroid anli injlomnut/Ot)' drugs
Protriptyline
Psora/ens
Sulfon.amides (bacteriostatic and
antidiabetic)
Tetracyclines (antibiotics)
n.a. - not available.
High
Medium
Medium
High
Low
High
High
Low
Mediun1
pbot.otoxic
photoallergic
phot.otoxic and
photoallergic
phototoxic
phototoxic
photoattcrgic
phototoxic
phot.otoxic
pbotoallergic
phototoxic
290-320 nm
290-400 nm
320-visible
Visible
340-430 nm
290-380 mn
290-400 nm
380-445 nm
300-400 mn
300-400 nm
320-400 nm
320-360 nm
310-340 om
290-320 nm
320-380 om
315-400 nm
350-420 nm
Health issues of ultraviolet tanning appliances e ICNIRP 123
al. 1989). The clinical improvement of atopic dermatitis
with sub-erythemal UV A exposure indicates that UVR is
able to modify substantially normal and pathological
immunological reactions. UVB radiation can promote the
development of skin cancer, perhaps by suppressing the
immune system allowing the tumor to escape immune
surveillance (Duthie et al. 1999). The action spectra in
the UVB for mixed lymphocyte reaction and mixed
epidern1al cell lymphocyte reaction were found to be
similar to the induction of thymine dimers upon DNA
irradiation (Hurks et al. 1995).
There is also evidence that exposure to UVR can
activate and accelerate the growth of human viruses
(Otani and Moti 1987; Perna et al. 1987), including
human immunodeficiency virus (HIV) (Zmudzka and
Beer 1990), and have effects on infectious disease
(Halliday and Norval 1997). At present, the significance
of these observations with respect to human health is
unclear. The effects of UV A exposure on the immune
system are even more unce1tain (Schwarz 1998; Vermeer
et al. 1998).
OCULAR EFFECTS
The cornea
The principal adverse effect of the absorption of
UVR (UVC and UVB) by the cornea is termed photo-
keratitis ("welder' s f1ash" or "snow-blindness"), and
damage is generally limited to the epithelial (front
surface) cells of the cornea (Sliney and Wolbarsht 1980).
After a 6- to 12-h latent period that depends inversely on
the sevetity of the exposure, there is severe corneal pain,
photophobia, lacrimation, and eyelid spasm. These
symptoms are terribly distressing (with incapacitation),
but typically resolve in 24 h. There is some evidence of
possible long-term effects of UVR absorption by the
cornea (Taylor et al. 1989) and evidence of endothelial
thinning (Pitts et al. 1987).
The lens
Transmission of UV A to the lens is much greater
than that of UVB. Animal data indicate that threshold
lenticular damage is limited mainly to UVR exposure in
the 295 to 325 nm wavelength band. Experimental
spectral efficiency for acute cataracts in laboratory ani-
mals has been measured only in this spectral region.
Although UV A sunbeds produce limited 295-325 nm
radiation, it should not be infeiTed that UV A is safe with
respect to lens exposure. Crystalline lens aging is char-
acterized in part by loss of elasticity and browning
(brunescence), both of which may be caused pa1tly by
UV A. Certain medicines may act as UV A photosensitiz-
ers of the crystalline lens.
The retina
At least for the chronic effects of exposure to solar
radiation and to radiation from conventional light
sources, the most important retinal damage mechanism is
photochemical injury from short-wavelength light
(Sliney and Wolbarsht 1980). The gradual brunescence
of the lens as it ages results in its decreased transmission
of blue-light and of UVR thereby affording increased
protection to the retina. Young children and people who
have had a lens surgically removed (aphakes) are at a
higher tisk of retinal damage from UVR and blue-light.
Until the last decade, many implanted artificial lens did
not effectively absorb UV A. Macular injuries to two
tanning booth users were mentioned in one study but not
confirmed (Walters and Kelley 1987).
The crystalline lens and cornea serve in considerable
measure to protect the retina from most UV tanning
booth radiation, even without protective goggles. As
discussed previously, the crystalline lens blocks UVR
below 400 nm and the comea blocks UVR below 300
nm, but trace amounts of UV -B radiation between 300
and 315 nm may reach the retina (Boettner and Wolter
1962; Sliney 1986).
Protective eyewear
The use of protective eyewear (goggles) will prevent
exposure of the eyes to harmful levels of UVR and
blue-light. This represents a very important issue for
sunbed exposures since an individual is normally pro-
tected from most of the overhead solar UVR by geomet-
rical shading by the brow ridge and upper lids. The
exposure from sunbeds is geometrically greatly different.
Furthermore, oblique rays can be focused into the nasal
equatotial region of the lens (Coroneo et al. 1991). UVR
can only reach the ctitically important germinative re-
gion of the lens by the focusing of oblique rays. Eyewear
that does not incorporate side protection is not suitable to
protect the eye from lateral UVR.
CONCLUSION AND RECOMMENDATIONS
A review of scientific evidence shows that solar
UVR is a cause of squamous cell cancer, basal cell
cancer, and cutaneous melanoma as well as causing
accelerated skin aging and other adverse health effects.
Because of this strong evidence on the adverse health
effects of UVR, even though there is not conclusive
direct evidence that sun bed exposure causes skin cancer,
it is ICNIRP's view that any use of suntanning appli-
ances is likely to raise the risk of cancer. This tisk is
particularly high for people having skin phototypes I and
II and for children.
124 Health Physics
/CNIRP, therefore, recommends against the use of
W-emitting appliances for tanning or other non-medical
purposes. The following groups are at particularly high
risk of incurring adverse health effects from UVR, and
therefore should be particularly counseled against the
use of tanning appliances:
People who have skin phototypes I or II;
Children (i.e., less than 18 y of age);
People who have large numbers of nevi (moles);
Persons who tend to freckle;
Individuals who have a history of frequent childhood
sunburn;
People who have premalignant or malignant skin
lesions;
People who have sun-damaged skin;
Those who are wearing cosmetics. These may enhance
their sensitivity to UV exposure; and
Persons taking medications. In this case they should
seek advice from their physician to determine if the
medication will make them UV -sensitive.
Although contrary to the above recommendation, if
persons decide to use suntanning appliances, steps should
be taken to minimize the risk. The recommendations
provided in Appendix A have been made by several
workshops, meetings, and publications which have
pointed to the identification of optical radiation hazards
associated with the development and popularity of the
"suntanning industry" (Council on Scientific Affairs
1989; ICNIRP/CIE Measurements of Optical Radiation
Hazards 1998; Miller et al. 1998; Moseley et al. 1998;
USNIH 1998; Greinert et al. 2001). ICNIRP generally
supports these recommendations as a likely means to
reduce the risk of skin cancers from the use of UV
tanning appliances and particularly to minimize the risks
for high-risk groups. Suggestions for fmther reading can
be found in Appendix B.
Acknowledgments -The support received by ICNIRP from the Interna-
tional Radiation Protection Association, the World Health Organization.
the International Labor Organization, the European Commission, and the
German Government is gratefully acknowledged.
During the preparation of this statement, the composition of the Jmema-
tional Commission on Non-Ionizing Radiation Protection was as follows:
A.F. McKinlay, Chairman (UK), Vice-chairman umil 2000
J.H. Bemhardr. Vice-chairmtm (Germany), Clwimum lmfil 2000
A. Ahlbom (Sweden)
U. Bergqvisr (Sweden) (j200J)
J. P. Cesarini (France)
M. Grwulolfo (/lilly), until 2000
F. R. de Gruijl (The Netherlands)
M. Hietanen (Finland)
R. Owen (USA)
D.H. Sliney (USA!
January 2003, Volume 84, Number I
J.A.J Stolwijk (USA), unril 2000
A. Swerdlow (UK). since 2000
L Szabo (Hungary), until 2000
M. Taki (Japan)
T.S. Tenforde (USA)
P. Vecchia (Italy). since 2000
B. Veyret (France), since 2000
R. Matthes. Scientific Secretary (Germany)
M.H. Repacholi. Chairman Emeritus (Swirzerlantl)
During the preparation of rhis docume/11, the composition of the ICNIRP
Standing Committee IV and task group was: D.H. Sliney (USA), Chairman
1-P. Cesarini (France) F. R. de Gruijl (The Netherlands) B.L. Diffey (U.K.)
M. Hietal!en (Finland) M.A. Mainster (USA) T. Okuno (Japan) B.E. Swck
(USA) A. Swerdlow (UK)
REFERENCES
Armstrong BK, Kricker A. Skin cancer. Dermatologic Clinics
13:583-594; 1995.
Autier P, Joarlette M, Lejeune F, Lienard T, AndreJ, Achten
G. Cutaneous malignant melanoma and exposure to sun-
lamps and sunbeds: descriptive study in Belgium. Mela-
noma Res 1:69-74; 1991.
Autier P, Dore JF, Lejeune F, Koelmel KF, Geffeler 0, Hille P,
Cesarini JP, Lienard D, Liabeuf A, Joarlette M, Chemaly P,
Hakim C, Koehl A, Kleeberg UR. (for the EORTC Mela-
noma Cooperative Group). Cutaneous malignant melanoma
and exposure to sunlamps or sunbeds: an EORTC multi-
center case-control study iJl Belgium, France, and Germany.
Int J Cancer 58:809-813; 1994.
Bech-Thomsen N, Ravnborg L, Wulf HC. A quantitative study
of the melanogenic effect of multiple suberythemal doses of
different ultraviolet radiation sources. Photodermatol Pho-
toimmunol Pbotomed 10:57- 64; 1994.
Bech-Thomsen N, Wulf HC. Photoprotection due to pigmen-
tation and epidennal thickness after repeated exposure to
ultraviolet light and psoralen plus ultraviolet A therapy.
Photodermatol Photoimmunol Photomed II :2 13-2 18;
1995.
Berg RJW, de Gruijl FR, van der Leun JC. Interaction between
ultraviolet A and ultraviolet B radiations in skin cancer
induction in hairless mice. Cancer Res 53:42 12-4217;
1993.
Bisset DL, Hannon DP, Orr TV. Wavelength dependence of
histological, physical and visible changes in chronically
UV -irradiated hairless mouse skin. Pbotochem Photobiol
50:763-769; 1989.
Boettner EA, Wolter JR. Transmission of the ocular media.
Invest Ophthalmol Vis Sci 1:776-783; 1962.
CIFJISO. Erythemal reference action spectrum and standard
erythemal dose. Geneva: ISO; ISO 17 166; 1999Nienna:
CIE; CIE S007/E; 1998.
CIE. Action spectrum for photocarcinogenesis. Vienna: CIE;
Report CIE 138-2000; 2000.
Cole CA, Forbes PD, Davies RE. An action spectrum for UV
carcinogenesis. Photochem Photobiol 43:275-284; 1985.
Coroneo MT, Mueller-Stolzenbury NW, Ho A. Peripheral light
focusing by the anterior eye and the ophthalmohelioses.
Ophthalmic Surgery 22:705-7ll; 1991.
Council on Scientific Affairs. Harmful effects of ultraviolet
Jight radiation. JAMA 262:380-384; 1989.
de Gruijl FR, Sterenborg HJCM, Forbes PD, Davies RE, Cole
C, Kelfken G, van Weelden H, Slaper H, van der Leun JC.
Health issues of ultraviolet tanning appliances e ICNIRP 125
Wavelength dependence of skin cancer induction by ultra-
violet irradiation of albino hairless mice. Cancer Res 53:53-
60; 1993.
de Gruijl FR, van der Leun JC. Estimate of the wavelength
dependency of ultraviolet carcinogenesis in humans and its
relevance to the risk assessment of a stratospheric ozone
depletion. Health Phys 67:314-325; 1994.
de Gruijl FR, Forbes PD. UV-induced skin cancer in hairless
mouse model. BioEssays 17:651-660; 1995.
Diffey BL. Use of UV A sun beds for cosmetic tanning. Br J
Dermatol115:67-76; 1986.
Dif'fey BL. Analysis of the risk of skin cancer from sunlight
and solaria in subjects living in Northern Europe. Photoder-
matol 4: 118-126; 1987.
Dif'fey BL, Farr PM, Ferguson J, Gibbs NK, de Gruijl FR,
Hawk JLM, Johnson BE, Lowe G, MacKie RM, Magnus
IA, McKinlay AF, Moseley H, Murphy GM, Nonis PG,
Young AR. Tanning with ultraviolet-A sunbeds. Br Med J
301:773-774; 1990.
Diffey BL, Jansen CT, Urbach F, Wulf HC. The standard
erythema dose: a new photo biological concept. Photoder-
matol Photoimmunol Photomed 13:64-66; 1997.
Duthie MS, Kimber I, Norval M. The effects of ultraviolet
radiation on the human immune system. Br J Derm
140:995-1009; 1999.
Eller MS, Ostrom K, Gilchrest BA. DNA damage enhances
melanogenesis. Proc Ntl Acad Sci USA 93:1087-1092;
1996.
Farr PM, Marks JM, Diffey BL, lnce P. Skin fragility and
blistering due to the use of sunbeds. Br Med J 296: 1708 -
1709; 1988.
Fitzpattick TB, Cesarini JP, Young A, Kollias N, Pathak MA.
Reported in Fitzpatrick TB, Bolognia JL. Human melanin
pigmentation: Role in pathogenesis of cutaneous melanoma.
ln: Zeise L, Chedekel MR, Fitzpatrick B, eds. Melanin: Its
Role in Human Photoprotection. Overland Park, KS: Val-
denmar Publishing Co; 1995: 177-182.
Gange RW, Park YK, Auletta M, Kagetsu N, Blackett AD,
Parrish JA, Action spectra for cutaneous responses to
ultraviolet radiation. In: Gange RW, Urbach F, eds. The
biological effects of UV A radiation. New York: Praeger;
1985:57-67.
Gies HP, Roy CR, Elliot G. Suntanning: Spectral irradiance
and hazard evaluation of ultraviolet sources. Health Phys
50:691-703; 1986.
Gilchrest BA, Park HY, Eller MS, Yaar M. Mechanisms of
ultraviolet light-induced melanogenesis. Photochem Photo-
bioi 63:1-10; 1996.
Gilchrest BA, Eller MS, Geller AC, Yaar M. The pathogenesis
of melanoma induced by ultraviolet radiation. N Engl J Med
340: 1341-1348; 1999.
Greinert R, McKinlay A, Breitbart EW. The European society
of skin cancer prevention-EUROSKIN: towards the pro-
motion and harmonization of skin cancer prevention in
Europe. Recouunendations Eur J Cancer Prev 10: 157 -162;
2001.
Halliday K.E, Norval M. The effect of UV on infectious
disease. Med Microbiol 8: 179-188; 1997.
Hersey P, MacDonald M, Henderson C, Schibeci S,
D'Alessandro G, Pryor M, Wilkinson FJ. Suppression of
natural killer cell activity in human by radiation from
solarium lamps depleted of UVB. J Invest Detmatol
90:305-3 10; 1988.
Higgins EM, du Vivier A WP. Possible induction of malignant
melanoma by sunbed use. Clin Exp Dermatol 17:357-359;
1992.
Hurks HMH, Out-luiting C, Vermeer PJ, Claas FHJ, Mommaas
AM. The action spectra for UV-induced suppression of
MLR and MECLR show that immunosuppression is medi-
ated by DNA damage. Photochem Photobiol 62:449-453;
1995.
Jones SK, Moseley H, MacKie RM. UV A-induced melano-
cytic lesions. Br J Dermatolll7:111-115; 1987.
!ARC. Solar and ultraviolet radiation. Monographs on the
evaluation of carcinogenic risk to humans. Vol. 55. Lyon:
International Agency for Research on Cancer; 1992.
ICNIRP/CIE. Measurements of Optical Radiation Hazards. A
reference book based on presentations by health and safety
experts on optical radiation hazards. Gaithersburg MD:
ICNIRP/CIE 6; 1998.
International Electtotechn.ical Commission. Safety of house-
hold and similar electrical appliances. Part 2: Particular
requirements for appliances for skin exposure to ultraviolet
and infrared radiation. Geneva: International Electrotecbni-
cal Commission; IEC 335-2-27; 1995.
Irwin C, Barnes A, Veres D, Kaidbey K. An UV radiation
action spectrum for immediate pigment darkening. Photo-
chem Photobiol 57:504-507; 1993.
Kadunce DP, Piepkom MW, Zone JJ. Persistent melanocytic
lesions associated with cosmetic tanning bed use: "sunbed
lentigines." JAm Acad Dermatol23:l029-1031; 1990.
Kligman LH, Kaidbey KH, Hitchens VM, Miller SA. Long
wavelength (> 340 nm) UV A-induced damage in hairless
mice is dose dependent. ln: Passchier W, Bosnjakovic
BFM, eds. Human exposure to ultraviolet radiatian: Risks
and regulations. An1sterdam: Elsevier Applied Science Pub-
lishers; 1987: 77- 8 I.
Lavker RM, Veres DA, Irwin CJ, Kaidbey KH. Quantitative
assessment of cumulative damage from repetitive exposures
to suberythemogenic doses of UV A in human skin. Photo-
chem Photobiol 62:348-352; 1995.
Ley RD. Ultraviolet radiation A-induced precursors of cuta-
neous melanoma in Monodelphis domestica. Cancer Res
57:3682-3684; 1997.
Ley RD, Applegate LA, Padilla RS, Stuart TD. Ultraviolet
radiation-induced malignant melanoma in Monodelphis do-
mestica. Photochem Photobiol 50: 1-5; 1989.
Lowe NJ, Meyers DP, Wieder JM, Luttman D, Borget T,
Lehman MD, Johnson A W, Scott IR. Low doses of repet-
itive ultraviolet A induce morphologic changes in human
skin. J Invest Dermatol L05:739-743; 1995.
McKinlay AF, Diffey BL. A reference action spectrum for
ultraviolet induced erythema in human skin. CIEJ 6: 17-22;
1987.
Miller SA, Hamilton SL, Wester UG, Cyr WH. An analysis of
UV A emissions from sunlamps and the potential impor-
tance for melanoma. Photochem Photobiol 68:63-70; 1998.
Moseley H, Davidson M, Ferguson J. A hazard assessment of
artificial tanning units. Photodermatol Photoimmunol Pho-
tomed 14:79-87; 1998.
Murphy GM, Wright J, Nicholls DSH, McKee PH, Messanger
AG, Hawk JLM, Levene GM. Sunbed-induced pseudopor-
phyria. Br J Dermatol 120:555-562; 1989.
Noonan FP, DeFabo EC. Ultrashort-B dose-response curves for
local and systemic immunosuppression are identical. Pho-
tochem Photobiol52:801-810; 1990.
Noonan FP, Recio JA, Takayama H, Duray P, Anver MR, Rush
WL, De Fabo EC, Merlino G. Neonatal sunburn and
melanoma in mice. Nature 413:271-272; 2001.
126 Health Physics
Otani T, Mori R. The effects of UV irradiation of the skin on
herpes simplex virus infection; Alteration in immune func-
tion mediated by epidermal cells and in the course of
infection. Arch Virol 96:1-15; 1987.
Parrish JA, Jaenicke KF, Anderson RR. Erythema and mela-
nogenesis action spectra of normal human skin. Photochem
Photobiol 36: 187-191; 1982.
Perna JJ, Mannix ML, Ronney JF, Notkins AL, Straus SE.
Reactivation of latent herpes simplex virus infection by
ultraviolet light: A human model. J Am Acad Detmatol
17:473-478; 1987.
Pierard GE. Ageing in the sun parlor. Int J Cos Sci 20:25 1-259;
1998.
Pitts DG, Bergmanson JPG, Chu LWF, Waxler M, Hitchins
VM. Ultrastructural analysis of corneal exposure to UV
radiation. Acta Ophthalmol (Copenh) 65:263-273; 1987.
Rivers JK, Norris PG, Murphy GM, Chu AC, Midgley G,
Monis J, Morris RW, Young AR, Hawk JLM. UVA
sunbeds: Tanning, photoprotection, acute adverse effects
and immunological changes. Br J Dennatol 120:767-777;
1989.
Robinson ES, Hill RH Jr, Kripke ML, Setlow RB. The
Monodelphis melanoma model: initial report on large ultra-
violet A exposures of suckling young. Photochem Photobiol
7 1:743-746; 2000.
Roth DE, HodgeS, Callen JP. Possible ultraviolet A-induced
lentigines: a side effect of chronic tanning salon usage.
J Am Acad Dermatol 20:950-954; 1989.
Salisbury JR, Williams H, du Vivier A WP. TalUling-bed
lentigines: Ultrastructural and histopathologic features.
JAm Acad Dermatol21:689-693; 1989.
Schwarz T. Effects of UV A light on the immune system. A
settled issue? In: Rougier A, Schaefer H, eds. Protection of
the skin against ultraviolet radiations. Paris: John Libbey
Eurotext; 1998: 93-95.
Seite S, Moyal D, RichardS, de Rigal J, Leveque JL, Hourseau
C, Fourtanier A. Effects of repeated suberythemal doses of
UV A in human skin. In: Rougier A, Schaefer H, eds.
Protection of the skin against ultraviolet radiations. Paris:
John Libbey Eurotext; 1998:47-58.
Setlow R, Grist E, Thompson K, Woodhead AD. Wavelengths
effective in induction of malignant melanoma. Proc Natl
Acad Sci USA 90:6666 - 6670; 1993.
Sliney DH, Wolbarsht ML. Safety with lasers and other optical
sources, a comprehensive handbook. New York: Plenum
Press; 1980.
Sliney DH. Defining biologic exposures to light. In: Cronly-
Dillon J, Rosen ES, Marshall J, eds. Hazards of light. New
York: Pergamon Press; 1986.
Spencer JM, Amonette RA. indoor tanning: Risks, benefits and
future trends. JAm Acad Dennatol33:288-298; 1995.
Sterenborg HJCM. Investigations on the action spectrum of
tumor genesis by ultraviolet radiation. Utrecht: State Uni-
versity of Utrecht; 1987. Dissertation.
Stern RS, Docken W. An exacerbation of SLE after visiting a
tanning salon. JAMA 255:3120; 1986.
Stern RS, Nichols KT, Vakeva LH. For the PUV A follow-up
study. N Engl J Med 336:1041-1045; 1997.
Swerdlow AJ, English JSC, MacKie RM, O' Doherty CJ,
Hunter JAA, Clark J, Mole DJ. Fluorescent lights, ultravi-
olet lamps, and risk of cutaneous melanoma. Br Med J
297:647-650; 1988.
Swerdlow AJ, Weinstock MA. Do tanning lamps cause mela-
noma? An epidemiologic assessment. J Am Acad Dermatol
38:89-98; 1998.
January 2003. Volume 84. Number I
Taylor HR, West SK, Rosenthal FS, Munoz B, Newland HS,
Abbey H, Emmett SK. Effect of ultraviolet radiation on
cataract formation. N Eng! J Med 319:1429-1433; 1989.
US National Institutes of Health. Program and abstract book-
Research workshop on risks and benefits of exposure to
ultraviolet and tanning. Bethesda: National Institutes of
Health; 1998.
Van Weelden H, de Gruij1 FR, van der Putte SCJ, Toonstra J,
van der Leun JC. The carcinogenic risks of modem tanning
equipment: Is UV-A safer than UV-B? Arch Dermatol
280:300-307; 1988.
Vermeer BJ, Winstzen M, Claas FHJ, Schothorst AA, Hurks
HMH. UV-induced immunosuppression. The critical role of
wavelength. In: Rougier A, Schaefer H, eds. Protection of
the skin against ultraviolet radiations. Paris: John Libbey
Eurotext; 1998: 89 -92.
Walter SD, Marrett LD, From L, Hertzman C, Shannon HS,
Roy P. The association of cutaneous malignant melanoma
with the use of sunbeds and sunlamps. Am J Epiderniol
131:232-243; 1990.
Walters BL, Kelley TM. Commercial tanning facilities: a new
source of eye injury. Am J Emerg Med 5:386-389; 1987.
Westerdahl J, Olsson H, Masback A, Ingvar C, Jonsson N,
Brandt L, Jonsson PE, Moller T. Use of sunbeds or
sunlamps and malignant melanoma in southern Sweden.
AmJ Epidem 140:691-699; 1994.
Westerdalll J, Olsson H, Masback A, lngvar C, Jonsson N.
Risks of cutaneous malignant melanoma in relation to use of
sun beds: futher evidence for UV -A carcinogenicity. Br J
Cancer 82: 1593-1 599; 2000.
Williams HC, Salisbury J, Brett J, du Vivier A. Sunbed
lentigines. Br Mecl J 296: 1097; 1988.
World Health Organization. WHO Environmental Health Cri-
teria 160. Ultraviolet radiation. Geneva: World Health
Organization; 1994: 140, 150, 224-225, 245-246.
Zmudzka BZ, Beer JZ. Activation of human immunodeficiency
by ultraviolet radiation. Photochem Photobiol6: 1153-1 162;
1990.
APPENDIX A
If tanning devices are used, then the following
specific recommendations from past workshops should
apply:
Claims of beneficial medical effects should not be
made. Any therapeutic use of tanning devices should
be clone only in medical units;
Tanning devices should comply with the requirements
of the IEC standard (1995) and be limited to UV type
1, 2, or 3 as defined in that standard;
Approptiate health warnings should be provided to the
client prior to tanning exposure;
Appropriate UV -protective goggles should be pro-
vided and worn during tanning exposures;
Operator staff should be provided with appropriate
approved training (receive appropriate certification);
Professional operators are responsible for providing
client information and guidance on the safe use of
tanning devices;
Health issues of ultraviolet tanning appliances e lCNIRP 127
Minimize the number of sessions. For example, the
French Regulations (J. 0. Republique Francaise, An-
nexe 2, 1997) require that regular exposure, for pho-
totypes Ill and IV, melano-competent skin, should not
exceed two sessions per week with a maximum of 30
sessions per year ( erythemaliy effective exposure of
500 J m
2
per session). An occasional break from the
regularity of exposure is advisable;
Manufacturers or dealers must supply exposure sched-
ules based on the tanning device lamp characteristics;
Because the sensitivities of individuals vary greatly, it
is advisable to limit the duration of the first session to
about one-half of a regular session in order to establish
the user' s skin response. If following the first session
any adverse reaction occurs, further use of the sunbed
should be discouraged;
Products designed to enhance or accelerate tanning
should not be used;
Any modifications, such as the replacement of lamps,
filters or reflectors should not change the IEC classi-
fication of the device. Tanning devices should have an
appropriate timer;
Tanning devices in hotels or in recreational facilities
should be subject to the same controls as noted above
(as for any commercial outlet);
Because of their possible misuse, unattended or coin-
operated tanning devices should not be used;
By the nature of their use, sunlamps in the home are
not subject to the same degree of control as those used
under proper supervision in commercial outlets, so
additional safety information should be provided by
the vendor or supplier of the tanning device. In these
circumstances only IEC type 3 tanning devices should
be used.
Recognizing that different countries will have different
ways of implementing and determining compliance
with these recommendations, the tanning facilities
should comply with these recommendations, and that
compliance should be checked by the appropriate
national authority where possible.
APPENDIX B
Further readings
American Academy of Detmatology. Position State-
ment on Indoor Tanning. Dermatology World; March
1999.
EUROSKIN Towards the Promotion and Harmoniza-
tion of Skin Cancer Prevention; Session VI: WHO
Workshop-UVR Tanning Devices, 2 - 5 May 2000,
Hamburg, Germany.
Finnish Center for Radiation and Nuclear Safety:
Guidance 1992.
IRPA/INIRC Guidelines. Health issues of ultraviolet
"A" sunbeds used for cosmetic purposes. Health Phys
61:285-288; 1991.
J. 0. Republique Francaise: Decret Nos. 97-6 17, Mai
1997 relatif a la vente et a la mise a disposition du
public de certains appareils de bronzage utilisant des
rayonnements ultraviolets.
Norwegian Radiation Protection Authority: Code of
practice (modification of #2 & 5 of the Royal Resolu-
tion concerning the use of x rays, 1983); 1992.
NRPB Board statement on effects of ultraviolet radi-
ation on human health and health effects from ultravi-
olet radiation. 6, No.2; 1995.
NRPB Use of Sunbeds and cosmetic tanning. State-
ment by NRPB Advisory Group on Non-Ionising
radiation. Radiological Protection Bulletin No. 2 18,
11-15; 1999.
Senat de Belgique (May 1998): Proposition de loi
reglementant 1' exploitation des centres de bronzage,
visant a responsabiliser les et les utilisa-
teurs de banes solaires (679/1).
Swedish Radiation Protection Institute: Regulatory
code concerning sunbeds (SSI FS 1998: 2).
U.S. Food and Drug Administration. Policy on maxi-
mum timer intervals and exposure schedule for sun-
lamps. August 1986; FDA Rockville MD, USA.
Radiation Protection Dosimetry-Ultraviolet Radia-
tion Exposure, Measurement and Protection.
lay AF, Repacholi MH, eds. Proceedings of an Inter-
national Workshop St Catherine' s College, Oxford,
England, October 18 -20; 1999. Radiation Protection
Dosimetry Vol. 91; 2000.
Indoor Tanning: The Risks of Ultraviolet Rays
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Indoor Tanning: The Risks
of Ultraviolet Rays

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http://www. f da .gov /ForConsu m ers/ConsumerU pdat es/u em 186687. htm# Tan ninginChildrenandTeens[ 12/1 /2009 8:47:49 PM]
Indoor Tanning: The Risks of Ultraviolet Rays
an assoc1at10n between mdoor tannmg and two types ot sKm cancer: squamous cell carcmoma
and melanoma
an association between UV-emitting tanning devices and cancer of the eye (ocular melanoma)
both UV-A and UV-B rays causing DNA damage, which can lead to skin cancer in laboratory
ammars ano numans
the risk of melanoma of the skin increasing bv 75 percent when tanning bed use started
before age 35
!ARC's review had some limitations, says Ron Kaczmarek, M.D., M.P.H., an FDA epidemiologist
wr1 o allcflyz-etllh e review. ttmttcrttcrrrs-;nd ode posstbl e ina c co
tanning experiences, not knowing the amount of UV radiation emitted by each tanning device,
a 11d tl1 e I nobi1rty-ta-s-e-parateLh-e-efferts-oHmnvit:luais'-imluo r a 11d ootduorexpusu , ".
Nevertheless..-IARC concluded tbat there is con.vlncing evidence o.Lan_as.s.o.ciati.o.tLhe.tw.e.e.o_the
use of indoor tanning equipment and melanoma risk, and that the use of tanning beds should
be discouraged.
"It's well established tbat !Bl radiation from tbe suo causes skio caocer.:...say.s Miller. "Since
lamps used in tanning beds emit UV radiation, the use of indoor tanning devices also increases
your nsK or sKm cancer.
back to too
Other Risks
In addition to the serious risk of skin cancer tanning can cause:
Premature aging. Tanning causes the skin to lose elasticity and wrinkle prematurely. This
after .
J'
immune svstem and the skin's natural defenses leaving vou more vulnerable to diseases
including skin cancer.
Gamage
rat;! i a tioR-m-ay- deve-1-0fHI-A-
itchy red rash and other adverse effects.
Advocates of tanning devices sometimes argue that using these devices is less dangerous than
'"UA-ta.r:u:ti.r.l.g-because....t.l:le
But there is no evidence to support these claims. In fact, sunlamps may be more dangerous
than the sun because they can be used at the same high intensity every day of the year-unlike
tl1e seasorr;-and cloud cmre .
back to top
Tanning in Children and Teens
FDA is particularly concerned about children and teens being exposed to UV rays. Intermittent
exposures to intense UV radiat1on leading to sunburns, espeCially in childhood and teen years,
increase the risk of melanoma, according to NCI.
FDA believes that limiting sun exposure and using sunscreen or sunblock are particularly
Important tor children smce these measures can prevent sunburn at a young age.
NL! reports that women who use tannmg beds more than once a month are percent more
likely to develop melanoma. Teenage girls and young women make up a growing number of
tannmg oea cuswmers.
roung peopre may noCffifi11<1hey are vulnerable to sk1n cancer," says Kaczmarek. 'Tfiey1lave

States who will learn they have melanoma this year, one out of eight will die from it, according
.o....N.C.l-estimat.es ..... _m pI" n"""" i <"
the second most common cancer in women 20 to 29 years old.
Some states are considering laws to ban those under age 18 from using tanning beds. And
many states now have laws that require minors to have a parent's consent or be accompanied
by a parent to the tanning facility.
FDA's current performance standard requires that a sunlamp product's label include a
recommended exposure schedule. FDA has advised manufacturers that this schedule should
,.... than tl'tfee-s-es-s-ions-ifrHte-fffs-t-wee .
In an NCI-sponsored study published in September 2009 in the Archives of Dermatology, the
study researchers h1red and tra10ed college students to pose as 15-year-oiO,ralr sKJOnea g1ns
dents as-keti-mer-e-th an 3, 69G4afl-A-. .
0
facilities in all 50 states about their practices.
Less than 11 percent onlle faCilities followed""F[)A's recommended exposure sclieaUie or mree
on
davs the first week, and many promoted frequent tanning with "unlimited tanning" discount
price packages.
I no
http://www. fda .gov /ForConsu m ers/ConsumerU pdates/u em 186687. htm# Tan ninginChildrenandTeens[ 12/1 /2009 8:47:49 PM]
Indoor Tanning: The Risks of Ultraviolet Rays
that "many parents are allowing their teens to tan and are providing written consent or
accompaniment."
"Parents should carefully consider the risks before allowing their children under 18 to tan," says
Miller.
back to top
FDA Regulation
FDA regulates radiation-emitting products, including sunlamps and products that contain them,
<:11rh ri<: trinniog beds aod bootbs aod po(table born..e_uoits Maoufactu(e(S of suolrimn<: m11c;t
comply with FDA regulations, including the performance standard for sunlamp products.
FDA requires sunlamp products to carry a warning label with specific information. Based on the
results of consumer testmg, FDA IS cons1denng amendmg the warnmg label requirements to
strengthen the warnings about skin cancer and irreversible eY-e dama!le
make the warning easier for consumers to read and understand
In a December 2008 Reoort to Congress FDA noted that FDA/NCI studies found that the UV
exposures typically provided by sunlamp products are excessive, and that comparable cosmetic
effects can be oroduced with exoosures that are onlv one-third or even one-fourth the levels
currently used. FDA is evaluating the results of this research and considering whether those
resui{S warram cnanges w its performance stam:t<rrtl for son1amp proouc{s.
J.ldCKlo lUf.l
The Riskiest Practices
FDA, NCI, the American Academy of Dermatology, and other health organizations advise limiting
exposure to natural UV radiation from the sun and avoiding artificial UV sources such as tanning
u e-cts-entirei y .
All use of tanning beds increases the risk of skin cancer. Certain practices are especially
dangerous. These include:
Failing to wear the goggles provided, which can lead to short- and long-term eye inj ury .
Starting with long exposures (close to the maximum time for the particular tanning bed),
which can lead to burning. Because sunburn takes 6 to 48 hours to develop, you may not
real ize your skin is burned until it's too late .
Failing to tallow manufacturer-recommended exposure times on the label tor your sKin type.
Tanning while using certain medications or cosmetics that may make you more sensitive to
UV rays. Talk to your doctor or pharmacist first.
back to top
Melanoma: One Woman's Story
17. She s-topped-
at age 20 when she was diagnosed with melanoma, the deadliest form of skin cancer. The
former Miss Maryland says she used tanning beds at least four times a week, and sometimes
every oay.
"Growing UJ2, until I started using tanning beds, m:t )2arents were very strict about me wearing
sunscreen," says Cicala. Although she also tanned in the summer sun during her 3 years of
ldrllrlll!;; ut:u u::.t:, '-''-d'd t:Stlmate-nhdr90-p-ercent of her was In tanning bt:u::.
ri.w:.i.ng-tl:l.ls- p.er i "ri
In the 4 years since she was diagnosed with melanoma, Cicala's surgeries have left her with
airour5 scars. etcola--gets<rheod-to-toe months, wllicl1 usually-results ;,
rP lllilll.d.LoLa_s.us.p.i.cio.us_gr.o vth
Th;" a test on a II En A-
regulated products.
uate-Po-stecf:-Norre-mbeJ -3(}, zfJrJ:T
u -a-ck-to-to-,...
I
1-
;
For More Information
1-
'
Sun Safety: Save Your Skin!
1-
I
Tanning
1-
i
Report to Congress: Labeling Information on the Relationship Between the Use of Indoor
!
Tanning Devices and Development of Skin Cancer or Other Skin Damage
1-
: What is Your Risk of Developing Skin Cancer? rlil
1-
.,1
http://www. fda .gov /ForConsu m ers/ConsumerU pdates/u em 186687. htm# Tan ninginChildrenandTeens[ 12/1 /2009 8:47:49 PM]
Indoor Tanning: The Risks of Ultraviolet Rays
Page Last Updated: 11 /30/2009
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http://www. f da .gov /ForConsu m ers/ConsumerU pdates/u em 186687. htm# Tan ninginChildrenandTeens[ 12/1 /2009 8:47:49 PM]
DEPARTMENT OF HEALTH&. HUMAN SERVICES
AJG 2 I 1986
Public Health Service
Food and Drug Adm1n1str at1on
875 7 Georgia Avenue
Silver Spring MD 209 1 0
TO: ALL MANUFACTURERS, IMPORTERS AND POTENTIAL MANUFACTURERS OF
SUNLAMP PRODUCTS.
POLICY ON MAXIMUM TIMER INTERVAL AND EXPOSURE SCHEDULE FOR
SUNLAMP PRODUCTS.
BACKGROUND:
The amended performance standard for sunlamp products (21 CFR 1040. 20) was
published in the September 6, 1985 issue of the Federal Register and will
become effective September 8, 1986. Any sunlamp product manufactured on or
after that date must comply with the amended standard.
The ten (10) minute maximum timer interval requirement was removed
from the original performance standard since there are newer
products on the market for which ten (10) minutes is not appropriate.
The maximum timer interval now depends on the intensity and spectral
distribution of ultraviolet (UV) radiation emission of each individual
model of sunlamp product and must not exceed the maximum recommended
exposure time provided on the required product warning label. Therefore,
sunlamp product manufacturers must develop an exposure schedule and
establish the maximum recommended exposure ttme (and therefore the
maximum timer interval) based on the characteristics of their particular
products.
The intended purposes of a sunlamp product timer are to provide
for reliable control of exposures and to limit acute (and delayed) damage
from unintentionally long exposures. However, the maximum timer setting
should also allow for selection of exposure times needed to build. up and
maintain a tan. The maxJmum timer interval is in no way to be considered
as a safe limit; all ultraviolet radiation is potentially hazardous.
The standard requires the manufacturer to provide an exposure schedule
in the product warning label. The purpose of the exposure schedule
is to allow a person to gradually build-up skin pigmentation and to
maintain a tan while controlling the risk of acute in.1ury and delayed
adverse effects. Since the UV radiation dose that causes a barely
discernible pink coloration (minimal erythemal dose or KED) is not the same
for different skin types, the exposure schedule for first time users will
depend on the skin type of the user. Furthermore, doses
of UV radiation received at 24 hours intervals initially lead to lowering
of the erythema and tanning thresholds. Therefore, the exposure schedule
and maximum recommended exposure time should be constrained by the
potential for erythema as well as the quantity of radiation necessary to
achieve and maintain a tan.
POLICY:
The Center for Devices and Radiological Health (CDRH) will use the
following criteria to evaluate the adequacy of the exposure schedule and
the recommended maximum exposure time (and therefore the maximum timer
interval):
Page 2
1) The maximum recommended exposure time (and maximum timer
interval) must not exceed a value which will result in an exposure
of four (4) times the minimal erythema dose (MED) for untanned
Type II skin (always burns, then tans slightly). This is based on
the CDRH Erythema Action Spectrum fproposed action spectrum of
Commission Internationale de L'Eclairage (CIE) modified by CDRHl.
See Appendix A for the action spectrum and weighting factors and
equations needed to derive it.
The formula for determining
time,"T" in seconds is:
e
the recommended maximum exposure
Te
!ViR!
where Standard MED 156J/Mt
vi = weighting factor
2
Ri irradiance in W/M
at 296nm
2) The recommended maximum exposure time must not exceed a value
which will result in an exposure of four (4) times the minimal
melanogenic dose (MMD) for untanned Type II skin. This is
based on the melanogenic action spectrum developed by Parrish
et al (1982). See Appendix B for this action spectrum.
The formula for determining the recommended maximum exposure time,
"T " in seconds is:
m
where standard MMD 459J/M
2
at 296nm
Ji weighting factor
2
irradiance in W/M
3) The recommended exposure schedule should provide for exposures
of no more than 0.75 MED three times the first week, gradually
increasing the exposure following weeks until aximua tanning
has occurred (approximate,ly four weeks total) and then provide for
maintenance of a tan by biweekly or weekly exposures of up to
four(4) MEDs or four(4) MMDs, whichever is less.
CDRH believes that the above criteria balances the need to limit acute (and
delayed) damages from unintentionally long exposure and the need to provide
for single exposure durations adequate to achieve and maintain a tan.
Appendices

E. Gundaker, Director
Office of Compliance
Center for Devices and
Radiological Health
......
.. ..._ ,._ .. . ...








.. .... ...
Appendix A
i$'rtAFT
[DATA)GIEL Y1l..B ER.Yll(EMA, Vi
CIE AC'IlON SPC'TRUM MODlFlED BY LYTLE (CORH) NORMAUZED TO 1 AT
250-302 NUMlT IS 156 11M2
WAVELENGTH READING
250 l 306 .:W99 362 .S39122E-03
251 1 307 .2692 363 .Sl9SOI&03
252 301 :1117 364 .S00607&03
253 309 . 1S92 365 .41239S&03
254 310 .1225 366 .464144&03
25S 311 .09419 367 .447931&03
2S6 312 .714399.01 361 .431636&03
251 313 . .S571991i..ol 369 .415931643
251 l 314 .4214998-41 3'10 .40018-03
259 l 3JS .03296 371 .3162107&03
2a)
l 316 . 25:J.4991i..o 1 3n .3'n14SB-03
261 I 317 .019S 373 .3SI59Q!.43
262 I 311 .01499 374 .:J.4S5318-03
263 1 319 .01153 37S
. .332t518-03 .
264 I 3210 .11719942 376 .32013SB-03
26S I 321 .612299B4'1 377 .3091S4B-Ol
~ I 322 .005141 m .l9719184J
267 I 323 .00403CS 379 .21'7QSI B4:J
261 I 324 .31CM9!JB.42 310 .2'76fOIS03
269 I 325 .212499&02 311 .266S3643
2'10 I 326 .204771641 312 .256121643
271 I 327 . 197331842 313 .247479B43
l'n I 321 . 190161641 314 .231469S43
273 I 329 .113159B-Ol 3IS .229'719643
%74 1 330 . 176f01S.C 316 .22142AS-43
%7S I 331 1'10171842 317 .2ll363S03
%76 I 332 . 161911S.C 311 .2QSSMB4S
rn I 333 . 151014641
-
. 191UlB4J
271 I 3:J.4 . IS2263S.C
,.,
. lto!JB.CD
279 1 33S .146123B.Ql 391 .li39UB O:J
210 1 336 . 141313B.Ql m .l77267Jl..O:J
211 1 337 .1362318-02 393 . 170121S03
212 1 331 . 1312118-01
,.
.164GB O:J
213 I 4339
.126SCISS.C
,
.1516ll&.o:J
214 I 340 .001219
"'
. IS215284l
215 1 :J.41 . ll7461S.C
,.,
.14129JB.O:J
216 1 :J.42 .11Sli3S.C
,.
.14193QJ.03
217 1 343 . 10901:J.B.02
,
.136T748.QJ
211 1 :J.44 .lQ!OIB.Ol 10 . l31184J
219 1 :us .t0126lS.C
""'
1
2tO 1 :J.46 .f757Sss.O:J
291 I :J.47 .940221&0:J
191 I 341 .!10591S&O:J
29J 1
,..,
.lntJB-03
2M l 3s0 .1411998-0:J
295 l 351 .11QSI2B.O:J
2t6 1 352 .7110'19S03
297 1 3S3 .7Sl6tf4J
-
1 354 .125254&43
299 1 3S5 .6JII5QIQJ
300 1
"'
.611419B4J
301 1 3S7 ~
301 1 351 .6252JB.CD
303 .7691 3S9 .6G253B-OJ
31M .5916 360 .SI06.0:J
305 .. us 361 .5S9417JI..O:J
"r'4
...., 1.0-01
..
c:x:
0
f-4 .
u
<

t:)
z
H
f-4
. . . ::r:
- t:)

-
Appendix B
(page 1)
WEIGHTING FACTORS FOR MELANOGENESIS, Ji

450 300 350 400

. WAVELENGTH (nm)
The MMD as function of wavelength has interpolated
(using log MMD) fromt the action spectrum for melanogenesis
of type II skin et al 1982)
PARRISH MELANOGENSIS T'fPE II
W1\ VEJ..EliiGTH Ji
( rrn)
250 .378409 302
251 . 374828 303
252 . 37124R 304
253 .367714 305
254 .364225 306
255 .360783 307
256 .35734 308
257 . 353943 309
258 .350547 310
.. 259 .347196 311
260 .343891 312
261 .340632 313
262 . 337419 314
263 .334206 315
264 .331039 316
265 . 327672 317
266 .327413 318
267 .326954 319
268 .326449 320
269 .32599 321
270 .325531 322
271 .325072 323
272 .324613 324
273 .324154 325
274 .323695 326
275 .323236 327
276 .321445 328
277 .319609 329
278 . 317865 330
279 .316075 331
280 .314285

332
281 .312541 333
282 .31075 334
283 .351694 335
284 .398008 336
285 . 450427 337
286 .509732 338
287 .576885 339
288 .652851 340
289 738778 341
290 .836088 342
291 . 861518 343
292 .887498 344
293 . 91435 345
294 .94212 346
295 .970625 347
296 1 348
297 .990959 349
298 350
299 .973287 'l"il
300 .96429 352
301 .886993 353
SKIN 1982
.815892
. 750391
. 690261
. 502296
.36551
.265997
.193565
.14087
. 102497
.745893-{)1
. 054301
. 395016E-<l1
.341137-Ql
.294593E-<ll
254384-Q 1
. 219683-{)1
. 189709-01
.163821-01
. 141467-01
. 122143-Qt
. 10i481E-Q1
.911137E-Q2
. 786745E-02
.679336-{)2
.586616-{)2

.437483-{)2
. 377812-{)2
.326265F:-Q2
. 281741-{)2
.243276P.-o2
.210089-{)2
.181447E-Q2
.176123-{)2
.170982E-Q2
. 165978E-Q2
.161113-{)2
.156385-{)2
.151841-{)2
. 147388E-Q2
.143074-{)2
,l38897E-<l2
.134A12E-D2
. l30864E-Q2
.127054E-Q2
.123336-{)2
.11971E-Q2
.116:>.22E-Q2
.ll2825C:-02
. l0952E-G2
. l0fi307E-Q2
. 103232-{)2
Appendix B
(page 2)
NOPAALI7.F.:n ro 296 t-1'-f
354 .100202- 0?.
35C) .972644-{)3
35n . 944186E-Q3
357 . 916645-{)3
358 . 890022-0.3
359 .S63859E-<l3
360 .A38613E-<l3
361 .813826-{)3
362 7A9958E-Q3
363 767007-{)3
3n4 .747729-03
365 .722942-<l)
366 .666q43E-<l3
367 .615075..()3
36R .567338E-Q3
369 .523272-{)3
370 .48288-{)3
371 . 44547-03
372 .4l0953P.-03
373 .379097-{)3
374 .34972-{)3
375 .322593-{)3
376 .297577-{)3
377 .274534-03
378 .253236-f))
379 .233591-{)3
380 .215506- 03
381 .213S32P.-Q3
382 .2115SaP.-oJ
3RJ .209963E-<l3
384 .207702-03
3es .2o5821E-03
386 . 203939-03
387 .202057-{)3
388 .20022l.E-Q3
389 .189296-{)3
390 .196594-{)3
391 .194R04E-G3
392 .193014E-Q3
393 . 191224E-Q3
394 .18948E-G3
395 .187735-{)J
396 .1A6037E-Q3
397 .184339-Q]
398 .18264E-Q3
399 .1aoqa8r.-o1
400 .179336E-Q3
401 . 1776A3E-Q3
402 .176077E-Q3
403 .17447-{))
.172A64E-Q3
40S .17l257E-o 3
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Randomized Trials of Antioxidant Supplementation for
Cancer Prevention: First Bias, Now Chance Next, Cause
Peter H. Gann
JAMA. publ ished onl ine Dec 9, 2008; (doi :1 0.1 001/jama. 2008.863)
http://jama.ama-assn.org/cgi/contentlfull/2008.863v1
Contact me if this article is corrected.
Contact me when this article is cited.
Vitamins E and C in the Prevention of Prostate and Total Cancer in Men: The
Physicians' Health Study II Randomized Control led Trial
J . Michael Gaziano et al. JAMA. 2008;0(2008):2008862.
Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers:
The Selenium and Vitamin E Cancer Prevention Trial (SELECT)
Scott M. Lippman et al. JAMA. 2008;0(2008) :2008864.
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- EDlTORIAL
Editorials represent the opinions
of the authors and lAMA and
not those of the American Medical Association.
Randomized Trials of Antioxidant
Supplementation for Cancer Prevention
First Bias, Now Chance-Next, Cause
Peter II . Gann, MD, cD
---------------------
I
N 1996, A WAVE OF !lOPE AROSE WHEN THE NUTRJTlONAL
Prevention of Cancer trial reponed a 65% reduction in
prostate in men receiving selenium supple-
mentatiOn. Thrs came only 2 years after the A TBC
(a-Tocopherol, l3eta Carotene) Cancer Prevention Trial had
reported a 3 5% reduction in prostate cancer occurrence among
men taking vitamin E supplements.
2
Suddenly, it appeared to
make sense that this cancer could be prevented by bolstering
antioxidant defenses in middle-aged and older men. Prostate
cancer was not a prespecified end point in either trial, and
although both results were based on post hoc analysis, random-
ization had worked and it seemed unlikely that the encourag-
ing findings were due to confounding bias. Indeed, confound-
ing stood as the likely explanation for discordance between the
earlier beta carotene trials that failed to demonstrate any ben-
efit and numerous observational smdies reporting that men who
consumed beta carotene-containing foods were at lower risk
for developing cancer, particularly those of the respiratory tract.
Now, 12 years later, comes the disappointing news that 2 ma-
jor trials conceived during the wave of hope found that neither
selenium nor vitamin E supplementation, alone or in combi-
nation, produced any reductions in prostate cancer or cancer
of any type. The results of these important studies, the SELECT
(Selenium and Vitamin E Cancer Prevention Trial) by Lippman
and colleagues and the Physicians' Health Study (PHS) IJ by
Gaziano and colleagues. are reported in this issue

Despite the null findings, it is important to recognize what
these trials have accomplished. SELECT had a simple, cost-
effective design, completed accrual of more than 35 000 par-
ticipants ahead of schedule-making it the largest individu-
ally randomized cancer prevention trial ever conducted-
and maintained high rates of adherence and retention for 4
to 7 years. Given its statistical power, it is unlikely that the
study missed detecting a benefit of even a very modest size.
The PHS II, \vith more than 14 000 male physicians, was also
remarkably well conducted and was especially noteworthy for
its cost-efficiency, with most of the study having been con-
ducted through the mail. Neither study has delivered its final
word on the blinded, randomized results. Preplanned sub-
group analyses are expected, particularly those aimed at base-
See also related articles.
2009 American Medical Associalion. All rights rcsei:'Ved.
line serum levels, smokingstams, and genetic factors that might
have modifi ed response. After that, like Voyager space probes,
each study will continue to contribute a wide range of valu-
able data as observational cohorts, before they fade away.
What can clinicians, researchers, and men concerned about
pros tate cancer prevention learn from the main results of these
phase 3Lrials? Three overarchingpoi.ntsare worth consideration.
Firs t, widespread use of prostate-specific antigen (PSA)
testing has s ubstantially restricted the design and interpre-
tation of prostate cancer prevention trials, perhaps perma-
nently. Neither trial mandated regular PSA testing; thus, end
points were determined by routine clinical management. This
greatly reduced the cost of each study; however, off-study
PSA testing was extremely common among these healthy,
motivated volunteers who had good access to care. In
SELECT, 83% to 86% of men reported receiving PSA tests
each year. Because of this intense surveillance, the geomet-
ric mean PSA at diagnosis was low ( <4.81 ng/mL) and, more
importantly, the proportion of cases with nonlocalized tu-
mors was very low. Of 1758 prostate cancers detected, at
diagnosis only 10 were extracapsular, l was regional node
positive, and 9 were metastatic. Even assuming that these
represent nonoverlapping cases, that would amount to only
20 nonlocali zed cancers, or L 1%. By comparison, among
l3 740 cases of pros tate cancer reported to the CAPSURE
database from 1990 to 2007, 3.7% were at clinical stage
T3bNOMO or greater, excluding T3a cases with extracap-
sul ar extension only.' Perhaps more strikingly, there was
only 1 death from prostate cancer in SELECT despite nearly
200 000 person-years of observation. Even allowing for the
requirement of a normal PSA and rectal examination at en-
try, that is an enormous deficit in expected mortality. Ap-
plying conservative assumptions about the exact age and fol-
low-up time distributions in SELECT, approximately 75 to
100 deaths would have been expected based on the US age-
specific prostate cancer mortality rates for 2000 through
2005.
6
There also were indications of a deficit in advanced
prostate cancer in PHS II, although a much smaller one.
How can an agent be shown to prevent serious, clinically sig-
nificant prostate cancers when PSA testing may be rapidly re-
moving those cancers from the population at risk before they
progress? The effects on early stage lesions may still be observed,
Author Affiliation: Department of Pathology. University of Illinois at Chicago.
Corresponding Author: Peter H. Gann, MD, SeD, Department of Pathology. Univer-
sity of Illinois at Chicago, 840 S Wood St, Chicago, IL 60612 (pgann@uic.edu).
(Reprinted) JAMA, Published onhne December 9, 2008 E1
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
EDlTORlAL
but if an agent has important effects on progression, those ef-
fects may be obscured. What to do? Trials could be conducted
only in populations that shun PSA testing, or mandatory biop-
sies could be performed after some reasonable interval of ex-
posure. Mandatory biopsies have the advantage of at least gath-
ering end points more quickly and also solve problems due to
the influence of an agent on PSA levels, as seen for finasteride
and now, apparently, statins.
7
Prostate cancer detection rates
are exquisitely sensitive to any factor that affects PSA levels, bi-
opsy rates, or biopsy sensitivity independent of an anticancer
effect. ln that regard, the nonsignificant increase in diabetes (pre-
sumably type 2) in the selenium group of SELECT deserves fur-
ther scrutiny because of the recognition that obesity has a small
suppressive effect on PSA and may have depressed prostate can-
cer ascertainment.
8
The increase in prostate cancer in the vi-
tamin E group, although not statistically significant (P= .06),
is also worrisome. However, this could have been due to a chance
elevation of the biopsy rate or biopsy sensitivity in that group,
and the absence of any prostate cancer increase in the combi-
nation group in SELECT or in PHS II is reassuring.
Second, single-agent interventions, even in combinations,
may bean ineffective approach toprimaryprevention in average-
risk populations. It may be time to give up the idea that the pro-
tective influence of diet on prostate cancer risk- which is clearly
observed in migrant studies and in populations transitioning
to a Western diet- can be emulated by isolated dietary mol-
ecules given alone or in combination to middle-aged and older
men. Evidence from the Prostate Cancer Prevention Trial sug-
gests that pharmacological inhibition of intraprostatic andro-
gen is capable of retarding the early growth of prostate cancers
9
Forcostandsafetyreasons, it is unreasonable, however, to rec-
ommend that all men begin takinga5a-reductase inhibitor daily
once they reach age 50 years. On the other hand, nonpharma-
cological dietary prevention of prostate cancer is probably more
complex and may involve certain inconvenient truths. Fortu-
nately, no dietary change this profound is likely to be benefi-
cial for prostate cancer alone. If it requires whole foods, extracts,
or dietary patterns, it may be necessary to give up the reduc-
tionist need to know which molecule is most responsible and
perhaps give up the notion of placebo controls as well. If it re-
quires starting eJ>rposure early in life and sustaining it for de-
cades, it may mean having to give up the idea of phase 3 trials
altogether. This does not mean that whole food or complex mix-
ture studies cannot be sound and biologically based. One can
start, for example, by asking how diet affects intra prostatic an-
drogen activity, a proven chemopreventive mechanism.
Third, it may be time to critically examine the methods
used to vet hypotheses for some phase 3 trials. In hind-
sight, and now with more recent information available, it
is easy to second-guess the rationale for these trials but more
difficult, and much more important, to determine how to
develop better phase 3 studies. Since the mid-l990s the tools
available for preclinical science, including new transgenic
models and genomic technologies, have vastly improved.
Phase 2 trials, which should be determining which few in-
E2 JAMA, Published online December 9, 2008 (Reprinted)
terventions make it through the pipeline, will improve as
intermediate end-point biomarkers become validated. More-
over, improvements in patient risk stratification, notably
through multi-single-nucleotide polymorphism genetic test-
ing,
10
will help design targeted trials with higher statistical
efficiency and more favorable risk-to-benefit ratios.
It now appears more likely that the unexpected results on
prostate cancer from the earlier selenium and vitamin E trials
were due to chance. In fact, the final report covering the entire
blinded treatment period of the Nutritional Prevention of Can-
cer Trial, published in 2003, found that for unexplained rea-
sons (chance), participants in theseleniumgroupwere less likely
than those in the placebo group, by 14% vs 35%, to undergo
biopsy when the PSA level was elevated.
11
After taking this into
account, the reduction in prostate cancer incidence was restricted
to the subgroup with low baseline PSA levels and the lowest
tertile of plasma selenium, a subgroup comprising fewer than
17 cases between treatment groups combined.
Epidemiology teaches that every statistical association bas
only 3 possible explanations: bias, chance, and cause. Regard-
ing nutritional prevention of prostate cancer, first-
generation phase 3 trials were too reliant on biased interpre-
tation of prior research; second-generation trials may have been
too reliant on chance; yet there is every reason to believe that
the next generation will have a firmer basis for causal hypoth-
eses. Until then, physicians should not recommend sele-
nium or vitamin E-or any other antioxidant supple-
ments-to their patients for preventing prostate cancer.
Published Online: December 9, 2008 (doi:10. 1001 /jama.2008.863)
Financial Disclosures: None reported.
REFERENCES
1. Clark LC, Combs GF Jr, Turnbull BW, et al; Nutritional Prevention of Cancer
Study Group. Effects of selenium supplementation for cancer prevention in pa
tients with carcinoma of the skin: a randomized controlled trial. lAMA. 1996:
276(24) 1957-1963.
2. The Alpha Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect
of vitamin E and beta carotene on the incidence of lung cancer and other cancers
in male smokers. N Eng/ 1 Med. 1994;330(15):1029 1035.
3. Lippman SM. Klein EA, Goodman PJ, et al. Effect of selenium and vitamin Eon
risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Pre-
vention Trial (SELECT). lAMA. doi:10.1001 /jama.2008.864.
4. Gaziano JM, Glynn RJ, Christen WG, et al. Vitamins E and C in the prevention
of prostate and total cancer in men: the Physicians' Health Study II randomized
controlled trial. lAMA. doi:10.1001/jama.2008.862.
5. Cooperberg MR, Cowan J, Broeri ng JM, Carroll PR. High-risk prostate cancer
in the United States. 1990-2007. World 1 Ural. 2008;26(3):211 -218.
6. Cancer statistics from the Surveillance, Epidemiology, and End Results (SEER)
program. National Cancer Institute, National Institutes of Health. http:/ /seer. cancer
.gov/statistics/. Accessed November 25, 2008.
7. Hamilton RJ, Goldberg KC, Platz EA, Freedland SJ. The influence ofstatin medi
cations on prostate-specific antigen levels. 1 Nat/ Cancer lnst. 2008;1 00(21):
1511-1 518.
8. Banez LL, Hamilton RJ, Partin AW, et al. Obesity-related plasma hemodil ution
and PSA concentration among men with prostate cancer. lAMA. 2007;298
(19):2275-2280.
9. Thompson IM , Goodman PJ, Tangen CM, et al. The infl uence of finasteride on
the development of prostate cancer. N Eng/ 1 Med. 2003;349(3):215-224.
10. Zheng SL. Sun J, Wiklund F, et al. Cumulative association of five genetic vari
ants with prostate cancer. N Eng/ 1 Med. 2008;358(9) :910-919.
11. Duffield-Lillico AJ, Dalkin BL, Reid ME, et al; Nutritional Prevention of Cancer
Study Group. Selenium supplementation. baseline plasma selenium status and in-
cidence of prostate cancer: an analysis of the complete treatment peri od of the
Nutritional Prevention of Cancer Trial. BlU Int. 2003;91 (7):608 612.
2009 American Medical Association. AU rights reserved.
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J ~
Online article and related content
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Effect of Selenium and Vitamin Eon Risk of Prostate
Cancer and Other Cancers: The Selenium and Vitamin E
Cancer Prevention Trial (SELECT)
Scott M. Lippman; Eric A. Klein; Phyllis J. Goodman; et al.
JAMA. publ ished online Dec 9, 2008; (doi :1 0.1 001/jama.2008.864)
http://jama.ama-assn.org/cgi/content/full/2008.864v1
Contact me if this arti cle is corrected.
This article has been cited 1 time.
Contact me when this article is cited.
Vitamins E and C in the Prevention of Prostate and Total Cancer in Men: The
Physicians' Health Study II Randomized Control led Trial
J . Michael Gaziano et al. JAMA. 2008;0(2008):2008862.
Randomized Trials of Antioxidant Supplementation for Cancer Prevention: First
Bias, Now Chance Next, Cause
Peter H. Gann. JAMA. 2008;0(2008) :2008863.
Email Alerts
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- ORIGINAL CONTIUBUTION JAMA-EXPRESS
Effect of Selenium and Vitamin Eon Risk
of Prostate Cancer and Other Cancers
The Selenium and Vitamin E Cancer Prevention Trial (SELECT)
Scott M. Lippman, MD
Eric A. Klein, MD
Phyllis J. Goodman, MS
M. Scott Lucia, MD
Tan M. Thompson, MD
Leslie G. Ford, MD
Howard L. T,arncs, MD
Lori M. Minasian, MD
J. Michael Gaziano, :MD, MPH
JoAnn Hartline, MPH
J. Kellogg Parsons, MD, MHS
James D. Bearden TTl, MD
E. David Crawford, 1\'ID
Gary E. Goodman, MD
Jaime Claudio, MD
Eric Winquist, MD, MSc
Elise D. Cook, MD
Daniel D. Karp, MD
Philip Walther, MD
M.ichael M. Lieber, 1\ID
Alan H. Kristal, DrPH
Amy K. Darke, MS
Kathryn B. Arnold, MS
Patricia A. Ganz, MD
Regina M. Santella, PhD
Demetrius Alhanes, MD
Philip H. Taylor, MD, SeD
Jeffrey L. Probstfield, MD
T. J. Jagpal, CCRP
John J. Crowley, PhD
FrankL. Meyskens Jr, MD
Laurence H. Baker, DO
Charles A. Coltman Jr, MD
See also related articles.
Context Secondary analyses of 2 randomized controlled trials and supportive epi-
demiologic and precl inical data indicated the potential of selenium and vitamin E for
preventing prostate cancer.
Objective To determine whether selenium, vitamin E, or both could prevent pros-
tate cancer and other diseases with little or no toxicity in relatively healthy men.
Design, Setting, and Participants A randomized, placebo-controlled trial (Sele-
nium and Vitamin E Cancer Prevention Trial [SELECD) of 35 533 men from 427 par-
ticipating sites in the United States, Canada, and Puerto Rico randomly assigned to 4
groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-bli nd
fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age
50 years or older (African American men) or 55 years or older (all other men), a serum
prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not
suspicious for prostate cancer.
Interventions Oral selenium (200 (Jg/d from L-selenomethionine) and matched vi -
tami n E placebo, vitamin E (400 IU/d of all rac-a-tocopheryl acetate) and matched
selenium placebo, selenium + vitamin E, or placebo + placebo for a planned fol-
low-up of minimum of 7 years and a maximum of 12 years.
Main Outcome Measures Prostate cancer and prespecified secondary outcomes,
including lung, colorectal, and overall primary cancer.
Results As of October 23, 2008, median overall follow-up was 5.46 years (range,
4.17-7.33 years). Hazard ratios (99% confidence intervals [Cis]) for prostate cancer
were 1.13 (99% Cl , 0.95-1.35; n=473) for vitamin E, 1.04 (99% Cl, 0.87-1 .24; n=432)
for selenium, and 1.05 (99% Cl, 0.88-1 .25; n =437) for selenium+ vitamin E vs 1.00
(n =416) for placebo. There were no significant differences (all P> .15) in any other
prespecified cancer end points. There were statistically nonsignificant increased risks
of prostate cancer in the vitamin E group (P= .06) and type 2 diabetes mellitus in the
selenium group (relative ri sk, 1.07; 99% Cl , 0.94-1.22; P=.16) but not in the sele-
nium + vitamin E group.
Conclusion Selenium or vitamin E, alone or in combination at the doses and formula-
tions used, did not prevent prostate cancer in this population of relatively healthy men.
Trial Registration clinicaltrials.gov identifier: NCT00006392
lAMA. 2009;301(1):(doi:10.1001/jama.2008.864)
P
ROSTATE CANCER MORTALITY LN
the United States has declined
in recent years, but this can-
cer remains the most com-
mon nons kin epithelial malignancy in
US men, with 186 320 new cases and
28 660 deaths (the second leading cause
www.jama.com
Author Affiliations are listed at the end of this
article.
Corresponding Author: Scott M. Lippman, MD, De-
partment of Thoracic and Head and Neck Medical On-
cology. University of Texas M . D. Anderson Cancer
Center, 1515 Holcombe Blvd, Uni t432, Houston, TX
77030-4009 (slippman@mdanderson.org), or Eric A.
Klein, MD, Cleveland Clinic Lerner College of Medi
cine, Desk A100, 9500 Euclid Ave. Cleveland. OH
44195 (kleine@ccf.org) .
2009 American Medical Association. All rights reserved. (Reprinted) JAMA, Published online Dewnber 9, 2008 E1
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
SELENIUM AND VITAMIN E FOR CANCER PREVENTION
of cancer death) estimated for 2008.
1
An effective prevention strategy for
prostate cancer would have substan-
tial public health benefits, including the
potential to reduce the incidence ofbio-
logically indolent prostate cancer,
which is significantly overdetected by
widespread screening with prostate-
specific antigen (PSA) and for which
most newly diagnosed men still un-
dergo curative-intent therapy involv-
ing substantial morbidity despite sur-
gical and other advances.
2

6
Important secondary results of 2 ran-
domized controlled trials, the Nutri-
tional Prevention of Cancer (NPC)
s tudy and the Alpha-Tocopherol, Beta-
Carotene Cancer Prevention (ATBC)
study, showed prostate cancer risk re-
ductions of 63% for selenized yeast and
32% for a -tocopherol (or vitamin E) J-to
ln addition, a large-scale randomized
controlled trialu involving several dif-
ferent regimens found that a combina-
tion of selenium, vitamin E, and beta
carotene reduced overall cancer mor-
tality. These clinical data, supported by
epidemiologic and preclinical data,
12
-
19
led to the design of the Selenium and
Vitamin E Cancer Prevention Trial
(SELECT)
1 0
Investigators in the United States and
Canada from major cooperative groups
of the National Cancer Institute and De-
partment of Veterans Affairs used the
Prostate Cancer Prevention Trial
(PCPT) accrual infrastructure (200
clinical sites, with 18 882 randomized
men) in designing and activating
SELECT. We report herein the effects
of selenium and vitamin E, alone or in
combination, on the risk of prostate
cancer and secondary end points in
SELECT.
METHODS
Study Design
SELECT is a phase 3 randomized, pla-
cebo-controlled trial of selenium (200
pg/d from L-selenomethionine), vita-
min E ( 400 lU/d of all rac-a-tocoph-
eryl acetate), or both (planned fol-
low-up of minimum of 7 years and
maximum of 12 years) for prostate can-
cer prevention. The major eligibility re-
quirements included age 50 years or
older for African American men and 55
years or older for all other men, no prior
prostate cancer diagnosis, 4 ng/mL or
less of PSA in serum, and a digital rec-
tal examination (DRE) not suspicious
for cancer. No current use of antico-
agulant therapy other than 175 mg/d or
less of acetylsalicylic acid or 81 mg/d
or less of acetylsalicylic acid with clo-
pidogrel bisulfate, no history of hem-
orrhagic s troke, and normal blood pres-
sure were also required because of
antiplatelet effects of vitamin E andre-
lated findings of the ATBC study.
Participant characteristics were based
on self:. report, including self-identification
of race and ethnicity which were defined
by the US Census Bureau. Race and eth-
nicity data were collected mainly for the
generalizability of trial results. All poten-
tially eligible men were required to pro-
vide written informed consent before
being allowed to participate in the trial.
The local institutional review board of each
study site approved the study for activa-
tion and reviewed its progress annually.
The trial was activated in july 2001 and
follow-up blinded to the trial results ended
on October 23, 2008.
Baseline blood and toenail speci-
mens and a 5-year blood sample were
collected for future biological studies.
Prostate tissue samples collected dur-
ing the trial were submitted for confir-
mation by central pathology review (no
samples were collected at baseline). Par-
ticipants without prostate cancer had
clinic visits once every 6 months
throughout the trial; with prostate can-
cer, annually. Adherence and adverse
events were monitored every 6 months
and a limited physical exami nati on in-
cluding assessments of blood pres-
sure, weight, and smoking status was
conducted annually. Prespecified ad-
verse events known to be associated
with vitamin E or selenium were graded
according to the National Cancer In-
stitute Common Toxicity Criteria.
Although eligible PSA and DRE re-
sults were r equired at study entry, an-
nual prostate cancer screemng with PSA
and DRE was not mandatory because
the benefits of this screening were un-
der debate when the trial opened and
community screening standards were
expected to change during the trial. Par-
ticipants were recommended during an-
nual clinic visits to undergo a PSA test
and DRE according to the s tandard of
care at their study sites and the partici-
pant' s preferences. A formal preran-
domization period (28-90 days; no pla-
cebo run-in capsules) gave potential
participants time to decide if they would
agree to stop disallowed over-the-
counter supplements of selenium or vi-
tamin E throughout the study and to
demonstrate, by returning for random-
ization, their willingness to adhere to
the trial. Other adherence methods in-
cluded offering each participant a free
multivitamin containing no selenium
or vitamin E and assessi ng serum lev-
els of vitamin E and selenium in all par-
ticipants at a subset of study sites (22
sites representing 7.8% of the trial
population). These sites were chosen
a priori to be representative of the broad
range of sites in the trial.
End Point Assessment
Participants reported prostate cancers
to the study site staff. Study staff ob-
tai ned medical records supporting the
diagnosis and abstracted the diagnos-
tic method and clinical stage. Tissue and
the corresponding pathology report
were sent to the central pathology labo-
ratory for confinnation. Gleason Score
was based on central pathology review.
Men were asked at their first 6-month
clinic visit to report new events since
entering the trial and thereafter to re-
port new events since their last visit.
Cardiac-event data were collected in de-
tail from the trial beginning (2001); data
on diabetes were added through self-
reported glitazone medication use (be-
ginning in 2003) and self-report of dia-
betes (beginning in 2005) via the
following question at each clinic visit:
"Does the participant report having dia-
betes (either his doctor told him he has
diabetes or he is taking medication for
diabetes)7"
A general question regarding any
events considered severe or life-
threatening (grade 3 or 4), regardless
E2 JAMA, Published online December 9, 2008 (Reprinted) 2009 American Medical Association. AU rights reserved.
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
of attribution to the study supple-
ments, was also asked. A Social Secu-
rity Death Index search was con-
ducted in july 2008 for participants who
had a last contact date of more than 18
months before the search. Other spe-
cifically queried events (known at study
inception to be related to either of the
study supplements) included alope-
cia, dermatitis, fatigue, halitosis, nail
changes, and nausea.
Statistical Analysis
The prin1ary end point was prostate can-
cer incidence as determined by routine
clinical management Cancers that were
not confirmed centrally were included
in the analysis. SELECT was designed as
a 4 group trial with 5 prespecified com-
parisons (selenium vs placebo, vitamin
E vs placebo, selenium + vitamin E vs
placebo, selenium vs selenium + vita-
minE, and vitamin E vs selenium + vi-
tamin E). With a sample size of 32 400
men, using a 1-sided a =.005 level
(equivalent to a 2-sided a=.01 level) ,
there was 96% power to detect a 25% re-
SELENIUM AND VTTAMIN E FOR CANCER PREVENTION
duction in prostate cancer for either of
the single agents ( vs placebo), 89% power
to detect a 25% reduction for selenium
+ vitamin E ( vs an active single agent)
and more than 99% power to detect a
44% reduction of selenium + vitamin E
(vs placebo).
Design assumptions were based on
the PCPT, ATBC, and NPC trials.
The details of the statistical design
have been described elsewhere
20
Important elements included (1)
constant accrual over 5 years; (2)
prostate cancer incidence in the pla-
cebo group based on PCPT for the
first 3 years and the 1995 Puget
Sound SEER registry afterward; (3)
adherence to the study supplements,
which was assumed to decrease over
the course of the trial with a 5-year
rate of 68% and 12-year rate of 51%;
(4) a constant 10% drop-in rate.
defined as participants receiving pla-
cebo who are taking active supple-
mentation off-study; (5) loss to
follow-up of 0.5% per year; and (6)
deaths estimated from PCPT for
years 1 to 3 and from the 1995 US
standard rates of men aged 63 years
and all races for year 4 onward. The
sample size was calculated to be
32 400 men and the number of pros-
late cancers expected in the placebo
group was 533 over l2 years. Under
the assumed conditions, the required
median time under observation was
estimated to be 8.8 years.
The primary analysis consisted of the
5 prespecified comparisons detailed
above. These comparisons allowed for
a meaningful analysis of the study re-
sults whether an interaction between vi-
tamin E and selenium occurred. Each
individual test was conducted at a
1-sided a =.005 level (equivalent to a
2-sided a =.01 level) using a Bonfer-
roni factor of 5 to preserve an overall
1-sided a=.00251evel (equivalent to a
2-sided a=.05 level) .
An independent data and safety
monitoring committee met yearly and
reviewed data on safety, adherence, and
diagnosis of prostate cancer. In addi-
tion to the flnal analysis, interim analy-
Figure 1. Flow of Participants Included in Analysis by Intervention Group
c
35533 Men randomized at 427 participating sites
~
~ . . . . . . .
----
8856 Randomized to receive placebo 8904 Randomized to receive vitam1n E + I 8910 Randomized to receive selenium 8863 Randomized to receive selenium
+placebo placebo + placebo +VItamin E
8696 Received placebo + placebo 8737 Received vitamin E + placebo 8752 Received selenium+ placebo 8703 Received selenium + placebo
as randomized as randomized as randomized as randomized
160 Excluded 167 Excluded 158 Excluded 160 Excluded
155 Removed from 2 156 Removed from 2 155 Removed from 2 155 Removed from 2
participating Sites {poor participating sites {poor participating sites (poor participating sites (poor
data and participant data and participant data and participant data and participant
management and management and management and management and
regulatory issues) regulatory issues) regulatory Issues) regulatory issues)
5 Ineligible 11 Ineligible 3 Ineligible 5 Ineligible
1 Had prior prostate 5 Had prior prostate 1 Had prior prostate 2 Had prior prostate
cancer cancer cancer cancer
4 Randomized in error 6 Randomized in error
1
2 Randomized in error 3 Randomized in error
{never received prope< (neve< received proper (neve< received proper (never received proper
informed consent) informed consent) informed consent) informed consent)
I
133 Clinically Ineligible" 128 Chrucally 1nehgible" I 1 t 3 CliniCally Ineligible' 113 Cfinicatly ineligible
154 Insufficient baseline data to completely 151 lnsufficoent baseline data to completely 1 66 Insufficient baseline data to completely 169 Insufficient baseline data to completely
evaluate dinicat ellgibllitl' evaluate clinical eligibility evaluate clinical eligibility evaluate clinical etig,bilitl'
420 Lost to fotlowup (last contact data 385 Lost to follow up Qast contact data
I
434 Lost to follow-up (last contact data 379 Lost to follow-up (last contact data
>24 mo before analysis)" >24 mo before analysis)< >24 mo before anatysis)
0
>24 mo before anatysis)
0
I
8696 Included in primary analysis
I
8737 lnctuded in primary analysis
I
8752 tnctlXled in ptimary analysis 8703 Included in primary analysis
aoue to increased blood pressure, highgrade prostatic intraepithelial neoplasia, suspicious digi tal rectal examination (DRE) or i ncreased prostate-specific antigen (PSA),
aspirin dosage, prior cancer less than 5 years before randomization, participation in another clinical trial . or other clinical reason.
bslood pressure, PSA, and/or DRE not performed within required time f rame (but normal) or other data-related reason.
cAll data up until the last contact are included; these men also could have been either clinically ineligible or had insufficient baseline data. For time-to-event analyses,
these men were censored at their last follow up.
2009 American Medical Association. All rights reserved. (Reprinted) JAMA, Published online Dewnber 9, 2008 E3
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
SELENIUM AND VITAMIN E FOR CANCER PREVENTION
ses were planned for years 5, 7, 9, 10,
and 11 after the first participant was
randomized; the percentages of the ex-
pected total number of prostate can-
cer events in the placebo group at each
interval were 14%, 35%, 61%, 7 4%, and
88%, respectively. Each interim analy-
sis resulted in recommendations that
could have included modifications to
the study, including termination of ac-
cntal , modifications to data collec-
tion, or early reporting of results. Rec-
ommendations were made to the
steering conm1ittee, which made the fi-
nal decisions.
The interim analyses tested the null
hypothesis at a 1-sided <X=.0005 level
(equivalent to a 2-sided a =. 001 level)
using the Cox proportional hazards re-
gression model. In addition, the alter-
native hypothesis of a 25% reduction in
prostate cancer incidence was tested at
a 1-sided level of a =.0005 (equivalent to
a 2-sided a=.001level) using an exten-
sion of the Cox proportional hazards re-
gression model that allows for testing a
relative risk (RR) not equal to l. The pur-
pose of the second analysis was to al-
low for the study to stop if it was deter-
mined that the expected reduction in
prostate cancer would not be observed.
The frequencies of the number of car-
diovascular events and cases of diabe-
tes were tested with a X
2
test. For car-
diovascular event and diabetes analyses,
we did not capture the report of the date
Table 1. Baseline Characteristics of Study Participants
of the event, which thus was not incor-
porated into the analysis.
Participants were randomized in a
randomized block scheme, in which
the block was the study s i te. This
ensured a balance of the 4 interven-
tion groups within each study site. All
analyses were performed by using an
intention-to-treat analysis in which
men were classified according to the
group to which they were random-
ized. All men were followed up until
death or loss to follow-up. For cancer
end points, men were censored at the
time of their last follow-up or death.
The analysis did not incorporate
adjustments for baseline covariates.
Data were analyzed by using SAS ver-
No. (%) of Participants
Placebo Vitamin E Selenium
Characteristics (n = 8696) (n = 8737) (n = 8752)
Age. y
Median (interquartile range) 62.6 (58.1 -67.8) 623 (58.0-67.8) 62.6 (58.2-68.0)
50-54 355 (4) 402 (5) 337 (4)
55-64 5078 (58) 5143 (59) 5076 (58)
6574 2702 (31) 2641 (30) 2733 (31)
<=;75 561 (6) 551 (6) 606 (7)
Race/ethnicity
White 6863 (79) 6890 (79) 6942 (79)
African American 1078 (12) 1107 (13) 1053(12)
Hispanic (non-African American) 492 (6) 477 (5) 481 (5)
Hispanic (African American) 76 (1) 103 (1) 86 (1)
Qther
8
187 (2) 160 (2) 190 (2)
Education (highest level)
s:High school graduate or GED 1993 (23) 1875 (22) 1917 (22)
Some college/vocational school 2291 (26) 2387 (27) 2327 (27)
<=;College graduate 4317 (50) 4394 (51) 4430 (51)
Unknown/missing 95 (1) 81 {1) 78(1)
PSA, ng/ml
0.1-1 .0 4122(47) 4208 (48) 4218 (48)
1.1-2.0 2728 (31) 2653(30) 2661 (30)
2. 1-3.0 1168 (13) 1228 (14) 1211 (14)
3.1-4.0 666 (8) 634 (7) 652 (7)
>4.0 5(<1) 3(<1) 2 (<1)
Unknown/missing 7 (< 1) 11 (<1) 8(<1)
Smoking status
Never 3682 (42) 3752 (43) 3780 (43)
Current 655 (8) 659(8) 631 (7)
Former 4208 (48) 4194 (48) 4214 (48)
Ever (unknown status) 63 (1) 55 (1) 61 (1)
Unknown 88 (1) 77 (1) 66 (1)
Abbreviations: GED, general equivalency diploma; PSA, prostate-specific antigen.
Sl conversion: To convert PSA to !Jg/l, multiply by 1 .0.
a o ther race/ethnicity include Asian (n= 420), Native Amencan (n = 99), Pacific Islander (n= 39), muniple races (n =34), and unknown (n = 1 1 9).
Selenium +
Vitamin E
(n = 8703)
62.4 (58.1-67.8)
385(4)
5052 (58)
2731 (31)
535 (6)
6874 (79)
1076 (12)
484 (6)
95 (1)
174 (2)
1898(22)
2348(27)
4372 (50)
85(1)
4213(48)
2666 (31)
1149(13)
659(8)
1 (<1)
15(<1)
3666(42)
670 (8)
4242 (49)
56 (1)
69(1)
E4 JAMA, Published online December 9, 2008 (Reprinted) 2009 American Medical Association. AU rights reserved.
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
sion 9.1 (SAS Institute Inc, Cary,
North Carolina).
Supplement Quality Control
and Quality Assurance
The Pharmacy Coordinating Center
received the study supplements for
bottling as finished capsules in
shipments containing lots of ac-
tive capsules along with the ap-
propriate matching placebo. As
required by current good manufac-
turing practice,ll each lot of capsules
was quarantined upon receipt until
testing was perfom1ed to ensure that
capsules labeled "active" by the
SELENIUM AND VITAMIN E FOR CANCER PREVENTION
manufacturer contai ned the ap-
propriate active agent and that cap-
sules labeled as "placebo" did
not contain an active agent. ln addi-
tion, each time the capsules were
bonled, production-run-verification
testing was performed to ensure that
bottles labeled as an active agent or
placebo contained the appropriate
material. To ensure that the quality
of the blind was maintained, cap-
sules received in each subsequent
lot were compared with the previous
lot and with matching capsules in
the current shipment for their char-
acteristics of weight, shape and size,
color and external marking, odor,
and comparability of contents of
opened capsules. Whether the par-
ticipant guessed or had an external
validation of whether he was getting
the active agent or placebo was not
assessed.
RESULTS
On September 15, 2008, the indepen-
dent data and safety monitoring com-
mittee met, reviewed data as of August
1, 2008, for the second formal interim
analysis, and recommended the discon-
tinuation of study supplements be-
cause the alternative hypothesis of no evi-
Tabl e 2. Adherence t o Study Supplements by Pill Counts and Bioadherence
% (Range)b
Pill Counts
8
Placebo Vitamin E Selenium Selenium + Vitamin E
Selenium/matching placebo
Year 1 (n=34 708) 85(76-85) 85 (77-85) 84 (76-84) 85 (77-84)
Year 2 (n =34163) 81 (72-81) 80 (72-81) 79 (71-80) 80 (72-80)
Year 3 (n=33616) 76 (68-77) 77 (69-77) 75 (68-76) 76 (69-77)
Year 4 (n=32976) 69(65-73) 73 (66-74) 71 (64-72) 72 (65-74)
Year 5 (n=23419) 69 (63-71) 71 (64-73) 69 (62-70) 70 (64-71)
Vitamin Elmatching placebo
Year 1 (n=34 708) 85(76-85) 85 (77-85) 85 (76-85) 85 (77-85)
Year 2 (n =34163) 80 (71-80) 80(71-80) 79 (70-79) 79 (71-80)
Year 3 (n=33616) 75 (67-75) 75 (67-76) 74 {67-75) 76 {69-77)
Year 4 (n=32976) 70 (63-72) 70 (63-72) 69 (62-71) 70 (63-72)
Year 5 (n=23419) 67 (61-69) 69 (62-71) 67 (61-69) 68 (61-70)
Median (lnterquartile Range)
Placebo Vitamin E Selenium Selenium + Vitamin E
Bioadherence (n = 285) (n = 290) (n = 277) (n = 257)
Serum selenium, IJ9/L
Baseline 137.6 (124.7-151 .8) 135.9 (122.4-148.4) 135.0 (123.4-145.9) 136.4 {122.9-150.0)
6-movisit 137.4 (123.3-152.0) 138.4 (124.1-154.0) 223.4 {198.6-251.8) 227.0 {199.4-251.2)
1st annual visit 138 1 (125.2-152.2) 137.7 (124.1-150.4) 232.4 (204.2261.4) 228.5 (205.5258.1)
2nd annual visit 132.0 (120.8-143.1) 129.8 (120.1-139.9) 228.0 (206.3256.9) 220.7 (194.0-249.5)
4th annual visit c 140.1 (124.3-150.8) 143.8 (126.2-158.6) 251.6 (218.7-275.0) 253.1 (21 0.5-283.0)
Cholesterol-adjusted a-tocopherol, J.lg/ml
Baseline 12.45 (10.70-1 4.95) 12.79 (10.69-15.37) 12.58 (10.43-14.75) 12.20 {10.12-15.35)
6-movisil 11.68 (1 0.09-13.61) 18.14 (15.21-22.45) 11.62 (10.1 0-13.44) 17.90 {15.11-20.84)
1st annual visit 11.68 (1 0.24-13.44) 18.50 (15.08-22.46) 11.69 (10.1013.03) 18.04 (14.77-22.35)
2nd annual visit 12.13 (10.80-13.72) 18.35 (15.1322.85) 11.80 (10.5713.58) 18.44 (15.32-22.89)
4th annual visit c 1209 (9.95-14.41) 16.57 (13.8622.61) 12.03 (9.57 - 13.53) 17.87 (14.68-22.31)
Cholesterol-adjusted -y-tocopherol, J-19/ ml
Baseline 1.31 (0.83-2.01) 1.43 (0.89-2.21) 1.50 (0.96-2.21) 1.44 (0.96-2.02)
6-movisit 1.50 (1.07 -1.97) 0.78 (0.51-1 .1 2) 1.64 (1.22-2.29) 0.74 (0.48-1.1 1)
1st annual visit 1.53 (1 .09-2.05) 0.75 (0.52 1.16) 1.69 (1.27 -2.33) 0. 70 (0.48- 1.04)
2nd annual visit 1.57 (1.13-2.13) 0.74 (0.49 1.08) 1. 76 (1.26-2.43) 0.66 (0.50-1.03)
4th annual visit c 1.69 (1.14-2.29) 0.80 (0.50-1 .23) 1.90 (1.48-2.70) 0.69 (0.47- 1.07)
Sl conversions: To convert serum selenium to IJmOI/L, multiply by 0.0127; a-tocopherol and -y-tocopherol to IJmoiiL. multiply by 23.22.
a Percentage of men adherent, defined as taking at least 80% of their study supplements. Denominators decrease over time reflecting the varying amounts of follow-up.
bThese ranges are estimates including those wfth missing data and assumes those missing were either all not adherent Qow estimate) or all adherent (high estimate).
cNumbers of participants for 4th annual visit are placebo (11= 79), vrtamin E (n= 78}, selenium (n= 72), and selenium+ vi tamin E (n= 71).
2009 American Medical Association. All rights reserved. (Reprinted) JAMA, Published online Dewnber 9, .WOS E5
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
SELENIUM AND VITAMIN E FOR CANCER PREVENTION
dence of benefit from either study agent
was convincingly demonstrated
(P< .OOOl) and there was no possibil-
ity of a benefit to the plam1ed degree with
Table 3. Clinically Diagnosed Prostate Cancers
additional follow-up. Study sites were no-
tified to discontinue supplements on Oc-
tober 23, 2008, and the data presented
in this article are current as of this date.
Participants
A total of 35 533 men were accrued and
randomly assigned at 427 participat-
ing sites in the United States , Canada,
No. (%)of Participants
Placebo Vitamin E
(n = 8696) (n = 8737)
Total No. of prostate cancers diagnosed by study site 416 473
Method of diagnoses
Prostate biopsy 404 (97) 458 (97)
Other/unknown 12 (3) 15 (3)
No. of total prostate biopsies 1020 1011
PSA tests
8
Year 1 6708 (83) 6876(84)
Year2 6641 (86) 6652 (85)
Year3 6284 (8S) 6334 (8S)
Year 4 6043 (8S) 6087 (84)
Year S 426S (84) 4246(84)
DRE tests
8
Year 1 S766 (72) S936(73)
Year 2 SS67 (72) 5S63 (72)
Year 3 S180 (70) 5188 (70)
Year4 4862 (69) 4823 (67)
Year s 3420 (68) 3418 (68)
Reason for biopsy (positive biopsies)
Increased PSA 259 (64) 324 (71)
PSA prompting biopsy, median (IQR), ng/ ml 4.60 (4.00-S.SO) 4.60 (3.995.60)
PSA velocity 12 (3) 10(2)
Abnormal DRE 66 (16) 58(13)
Increased PSAIPSA velocity + abnormal DRE 55 (14) 49 (1 1)
Other 8 (2) 13(3)
Tstage
T1a-c 278 (70) 343 (75)
T2a-b 122 (30) 114 (25)
T3a-b 0 (0) 2 (0)
TX/not staged 16 14
N stage
NO 109 (100) 127 (100)
N1 0 (0) 0(0)
NX/not staged 307 346
Mstage
MO 124 (100) 134 (99)
M1a-b 0 (0) 2 (1)
MX/not staged 292 337
Gleason scoreb
No. graded by central laboratory 365 396
2-6 240 (66) 249 (63)
7 (grade 3 + grade 4) 80 (22) 97 (24)
7 (grade 4 + grade 3) 21 (6) 27 (7)
8-10 24 (7) 23(6)
Abbreviations: ORE, digital rectal examination: lOR, interquartile range; PSA, prostate-specific antigen.
Sl conversion: To convert PSA to J.Jg/L, multiply by 1.0.
Selenium +
Selenium Vitamin E
(n = 8752) (n = 8703)
432 437
419(97) 420(96)
13(3) l7 (4)
982 997
6807 (84) 6838 (84)
6635(8S) 6673(86)
6376(8S) 6349(8S)
606S(8S) 604S (84)
4271 (84) 42S7 (84)
S870(72) 5833(72)
5S61 (72) 5591 (72)
5198(70) 5190 (70)
4878(69) 4878(68)
3397 (68) 3425(68)
296 (71) 263(63)
4.83 (4.05-5.70) 4.70 (4.00-5.60)
13(3) 16 (4)
46(11) 56(13)
56(13) 72 (17)
12 (3) 17 (4)
301 (73) 286(69)
108(26) 128(31)
5 (1) 3 (1)
18 20
125 (99) 117 (100)
1 (1) 0(0)
306 320
122 (96) 119(98)
5(4) 2 (2)
305 316
361 365
217 (60) 220(60)
105 (29) 91 (25)
19(5) 24 (7)
20(6) 30(8)
a Percentages are based on alive participants who are prostate cancer-free and for whom the form was submitted.
bGieason score was based on central pathology review. The Gleason grade ranges from 1 to 5, with 5 having the worst prognoSis. The Gleason score ranges from 2 to 10, wrth 1 0
t1aving the worst prognosis.
E6 JAMA, Published online December 9, 2008 (Reprinted) 2009 American Medical Association. AU rights reserved.
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
and Puerto Rico between August 22,
2001 , and june 24, 2004. FIGURE l
s hows the SELECT randomization
scheme including participants who
were excluded from analyses; all 621
participants at 2 study sites were re-
moved from the analysis because of se-
vere problems that were detected early
on including poor data and partici-
pant management and regulatory is-
sues. These participants differed sub-
stantially from the rest of the SELECT
population in being from sites in the
south of the United States, 99% Afri-
can American, younger (median age 57
years), and of a lower education level
( 6 7% had < high school education), and
in having lower PSA levels (57% bad
< l.O nglmL) and a higher prevalence
of current smokers (33%) An addi-
tional9 participants were removed be-
cause they were found to have had pros-
tate cancer at randomization and 15
were removed because their informed
consent was never received. More men
were accrued (35 533 in 3 years) than
initially planned (32 400 in 5 years)
mainly because of a faster - than-
expected accrual rate and the admin-
istrative time it takes to close down
accrual.
The baseline characteristics of
SELECT participants by each of the 4
groups (placebo, vitamin E, selenium,
and selenium + vitamin E) are shown
in TABLE 1. All potentially important
risk factors were well balanced among
the groups. A total of 2.6% of SELECT
men were former PCPT men random-
ized to finasteride; during the trial,
4.8% of the non-PCPT participants
reported use of finasteride at 5 mg
(n=1602) or 1 mg (n=86).
The median overall follow-up was
5.46years (range, 4.17-7.33 years). The
percentages of participants with a re-
cent last-contact elate were more than
88% within 7 months and 92% within
l3 momhs of the SELECT data analy-
sis. loss to follow-up, defined as hav-
ing a last contact date of more than 24
months before analysis, involved 5.1%
of participants, which was higher than
had been estimated for the trial design
(3.5% at 7 years after trial activation).
SELENIUM AND VITAMI N E FOR CANCER PREVENTION
Figure 2. Cumulative Incidence of Prostate Cancer Detected Each Year by Intervention
Group
0.08
Placebo
0.07 ------Vitamin E .--
0.06
---Selenium , ./ ~
--Selenium+ vitamin E , --
j;-
0.05
'0
,/ /
.. ... ,.-'' ;
'
"'
0.04
.0
0.03
0.02
0.01
__ ... ' / . / , ..... !
0 2 3 5 6
Years After Randomization
No. at risk
Placebo 8689 8553 8328 8039 7389 4892 2516
Vitamin E 8732 8610 8373 8098 7401 4867 2537
Selenium 8750 8597 8341 8083 7393 4848 2558
Selenium + vitamin E 8700 8585 8371 8097 7428 4894 2580
Compared with placebo, there was a statistically nonsignificant increase in prostate cancer in the vitamin E
group (P=.06) and not in the selenium + vitamin E group (P=.52) or the selenium group (P=.62).
Adherence to both study agents as de-
termined by pill count was similar across
all study groups, and averaged 83% at
year land 65% at year 5. Adherence to
atleast1 of the 2 agents was 87% at year
1 and 72% at year 5 (the design-
estimated adherence rates were 90% at
year l and 68% at year 5) . Bi.oadher-
ence was measured in a subset of par-
ticipants by serum levels of selenium and
cholesterol-adjusted a-tocopherol and-y-
tocopherol (which is suppressed by a-
tocopherol) and showed a good separa-
tion in agent serum levels between the
groups (TABLE 2). The drop-in rate was
assessed by a direct question to the par-
ticipants about taking either of the
supplements. Positive responses were
3.1% or less for vitamin E and 1.8% or
less for selenium in each year (below the
design drop-in estimate of 10%). Pros-
tate tissue samples were sent to the cen-
tral pathology laboratory for confirma-
tion in 86% of cases. The central
laboratory agreed with the clinical site's
prostate cancer diagnosis in 99% of these
cases.
Prostate Cancer
There were no statistically significant dif-
ferences in the rates of prostate cancer
between the 4 groups (placebo, 416 cases
[5-year rate of 4.43%); selenium, 432
cases [4.56%]; vitamin E, 473 cases
[4.93%]; selenium + vitamin E, 437
cases [4.56%]) (TABLE 3 and fiGURE 2).
Compared with placebo, the hazard ra-
tios (HRs) for prostate cancer were 1.13
(99% confidence interval [ Cl], 0.95-
1.35; 95% CI, 0.99-1.29; P= .06) in the
vi tamin E-alone group, 1.05 (99% CI,
0.88-1.25; 95% CI, 0.91-1.20; P=.52)
in the selenium + vitamin E group, and
1.04 (99% Cl, 0.87-1.24; 95% Cl, 0.90-
L 18; P= .62) in the selenium-alone
group. The data and safety monitor-
ing committee had some concern over
the s tatistically nonsignificant in-
crease in prostate cancer in the vita-
min -alone group (P= .09 per interim
data of August 1, 2008) and over a non-
significant increase in diabetes melli-
tus associated with selenium (P= .08 per
interim data of August l , 2008).
The majority of prostate cancers di-
agnosed during the trial were early-
stage and low-grade, and cancer stage
and grade were similar across all groups
(Table 3). The percentage of patiems
who had an annual PSA examination
and DRE was similarly high and the bi-
opsy rate was similar across all groups,
indicating that the prostate cancer find-
ings were not due to screening-
associated detection bias. More than
95% of prostate cancers were cliag-
2009 American Medical Association. All rights reserved. (Reprinted) JAMA, Published online Dewnber 9, 2008 E7
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
SELENIUM AND VITAMIN E FOR CANCER PREVENTION
nosed by biopsy, the triggers for which
(based on PSA and other factors) are
shown in Table 3 and were similar
across all groups. The number of pros-
tate cancers in the placebo cohort was
higher than what was estimated at study
inception. This was due to the faster
than expected accrual, the larger than
expected sample size, and higher base-
line PSA levels than anticipated.
Secondary Outcomes
There were no significant differences
(all P> .15) in any prespecified second-
ary cancer end points (FIGURE 3 and
TABLE 4). At 5 years, the cumulative
death rate in the placebo group was 38
deaths per 1000 participants (95% Cl,
34 deaths per 1000 participants to 42
deaths per 1000 participants) ; the es-
timated rate at trial inception was 48
deaths per 1000 participants. The num-
bers of deaths from any cause were simi-
lar across the 4 groups (382 in pla-
cebo group, 358 in vitamin E group,
378 in selenium group, and 359 in se-
lenium + vitamin E group).
The study agents had no significant
effects on the overall incidence of car-
diovascular events (Table 4). A statis-
tically nonsignificant increase in type
2 diabetes mellitus (diagnosed after ran-
domization) occurred in the selenium-
alone group vs placebo group (n= 724;
10.0%; 99% Cl, 9.1%-11.0%; VS n=669;
9.3%; 99% Cl, 8.5%-10.2%, respec-
tively; RR, 1.07; 99% CI , 0.94-1.22;
P=.l6). The number (percentage) of
cases of diabetes mellitus was 700
(9.7%; 99% Cl, 8.8%-10.6%) in the vi-
tamin E group and 660 (9 1 %; 99% Cl,
8.2%-10.0%) in the selenium + vita-
min E group (P values of these data
compared with placebo were 0.47 for
vitamin E and 0.61 for selenium + vi-
tamin E). Data on known, clinically less
significant adverse effects of the study
agents (alopecia, dermatitis, halitosis,
Figure 3. Cumulative Incidence of Lung Cancer, Colorectal Cancer, All Other Primary Cancers, and Deaths by Intervention Group
Lung Cancer Colorectal Cancer
0 .020 0.020
0.018
Placebo
0.018
VitaminE
0.016 ---Selenium 0.016
0.014
--Selenium+ VItamin E
0.0 14
0.012 ,r 0.012
ii
r
'0
"'
0.010
"'
0.010
.0 .0
2 2
.:..:-
0.
0.008
0.
0.008
-
0.006 0.006 ::::::F-.r.r-;!;--3'-
0.004 0.004
0.002 0.002
0 2 3 5 6 0 2 3 5 6
Years Alter Randomization Years After Randomization
No. at risk No. at risk
Placebo 8689 8577 8440 8224 7602 5087 2626 Placebo 8689 8571 8431 8207 7582 5068 2613
Vitamin E 8732 8630 8491 8290 7647 5073 2649 Vrtamin E 8732 8628 8476 8277 7625 5062 2641
Selenium 8750 8621 8447 8257 7597 5010 2657 Selenium 8750 8615 8432 8240 7576 5000 2648
Selenium+ vitamin E 8700 8598 8457 8264 7647 5067 2674 Selenium + vitamin E 8700 8597 8447 8245 7629 5050 2655
All Other Cancers Deaths
0.08 0.08
O.D7 O.D7
0.06 0.06

0.05

0.05
n
"'
0.04
"'
0.04
.0 .0
2 2
0. 0.03 0. 0.03
0.02 0.02
0.01 0.01
0 2 3 4 5 6 0 2 3 4 5 6
Years Alter Randomization Years Alter Randomization
No. at risk No. at risk
Placebo 8689 8532 8362 8 113 7466 4977 2553 Placebo 8689 8585 8454 8236 7617 5100 2631
Vitamin E 8732 8602 8427 8190 7518 4954 2578 Vitamin E 8732 8639 8505 8310 7662 5086 2653
Selenium 8750 8587 8378 8160 7488 4913 2594 Selenium 8750 8628 8460 8277 7622 5029 2667
Selenium+ vitam<n E 8700 8557 8398 8176 7529 4972 2610 Selenium + vitBmJn E 8700 8610 8475 8285 7679 5089 2684
There were no significant differences in any prespecified secondary cancer or death end points (all P> .15). The blue portions of they-axes indicate 0 to 0.02 cancer probability.
ES JAMA, Published online December 9, 2008 (Reprinted) 2009 American Medical Association. AU rights reserved.
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
SELENIUM AND VITAMIN E FOR CANCER PREVENTION
nail changes, fatigue, and nausea) are continued early (in year 7 of the overall rate, and loss to follow-up were largely
s hown in TABLE 5. The only statisti- 12-yearstudy) in accordance with a unani- met and gave the trial significant power
cally s ignificant di ffe rences (P<.Ol) mous recommendation of the data and to detect the estimated preventive ef-
were for selenium vs placebo for alo- safety monitoring committee stating that, fects . Furthermore, the large sample
pecia and grade.s 1 to 2 dermatitis. based on the evidence to date from the size, inclusion of a substantial propor-
COMMENT
7-year planned interim analyses, there was lion of non-white men, and equal dis-
no evidence of a benefit from either study tribution of known risk factors across
ln SELECT, neither 200 pg of selenome- agent and no possibility of a benefit to all trial gr oups make the conclusions
thionine or 400 IU of synthetic DL a- the pla1med degree with additional follow- drawn from SELECT especially ro-
tocopherol, given orally alone or combined up. Sensitivity analyses suggested that the bust and generalizable.
for a median of 5.5 years had significant prespecifiecl25% risk reduction was ex- Why were selenium and vitamin E in-
effects on the primary or secondary end tremely unlikely to be reached for either effective in preventing prostate cancer in
points. A statistically nonsignificant in- agent even with additional exposure. SELECT despite strong secondary evi-
creased incidence of prostate cancer The statistical assumptions made in dence suggesting efficacy?
7

8
Consider-
(P= .06) was observed in the vitamin E SELECT involving accrual rate, study ing selenium fi rst, the secondary reduc-
group but not in the selenium + vi tamin s uppl ement adherence and drop-in tion in prostate cancer incidence in the
E group. The trial supplements were dis- rates, prostate cancer incidence, death NPC study could have been subj ect to
Tabl e 4. Secondary O utcomes Including Diagnosis of Other Primary Cancers, Diabetes, Cardiovascular Events, and Deaths a
Placebo Vitamin E Selenium Selenium + Vitamin E
(n = 8696) (n = 8737) (n = 8752) (n = 8703)
No. HR No. HR No. HR No.
of Men (99% Cl) of Men (99% Cl) of Men (99% Cl) of Men
Any cancer (including prostate)b 824 1 (Reference] 856 1.03 (0.91-1.17) 837 1.01 (0.89-1.15) 846
Lung 67 1 (Reference) 67 1.00 (0.64- 1.55) 75 1. 12 (0.73- 1.72) 78
Colo rectal 60 1 (Reference] 66 1.09 (0.69-1. 73) 63 1.05 (0.66-1.67) 77
Other primary cancer
0
306 1 (Reference] 274 0.89 (0.72- 1.10) 292 0.95(0.77-1.1 7) 290
No. RR No. RR No. RR No.
of Men (99% CI) of Men (99% Cl) of Men (99% Cl) of Men
Diabetesd 669 1 (Reference] 700 1.04 (0.91-1.18) 724 1.07 (0.94-1.22) 660
Cardiovascular events
Any (including death) 1050 1 (Reference] 1034 0.98 (0.88-1.09) 1080 1.02 (0.92-1.13) 1041
Nonfatal strokes
Hemorrhagic 11 1 (Reference] 7 0.63 (0.18-2.20) 11 0 99 (0.33-2.98) 12
Ischemic 56 1 (Reference] 49 0.87 (0.53-1 .44) 51 0.90 (0.55-1.49) 67
Not specifiede 25 1 (Reference] 14 0.56 (0.24-1.32) 11 0.44 (0.17-1.1 1) 20
Ot her nonfatal (worst grade)
1
Grade3 626 1 (Reference] 642 1.02 (0.89-1. 17) 685 1.09 (0.95-1.25) 624
Grade4 190 1 (Reference] 203 1.06 (0.82- 1.38) 193 1.01 (0.78-1.31) 201
No. HR No. HR No. HR No.
of Men (99% CI) of Men (99% CI) of Men (99%CI) of Men
Deaths 382 1 (Reference] 358 0.93 (0.77-1.13) 378 0.99 (0.82-1.1 9) 359
Cancer 125 1 (Reference] 106 0.84 (0.60-1 . 18) 128 1.02 (0.74-1.41) 117
Prostate 0 1 (Reference] 0 NA NA 0
Lung 41 1 (Reference] 38 0.92 (0.52-1.65) 45 1.10 (0.63-1.91) 39
Colorectal 10 1 (Reference] 13 1.30 (0.44-3.83) 10 1.00 {0.32-3.1 6) 15
Other primary cancer
0
74 1 !Reference] 55 0.74 (0.47- 1.17) 72 0.97 (0.63 1.49) 63
Cardiovascular 142 1 !Reference] 119 0.84 (0.61-1.15) 129 0.91 (0.66-1.24) 117
Hemorrl1agic stroke 8 1 (Reference] 9 1.12 (0.32-3.92) 9 1.12 (0.32-3.93) 12
Other cardiovascular 134 1 (Reference] 110 0.82 (0.59-1.14) 120 0.89 (0.65- 1.24) 105
Other deaths 115 1 !Reference] 133 1. 15 (0.83-1.60) 121 1.05 (0.75-1.47) 125
Abbreviations: Cl. conlidence u1tervaJ: HR. hazard ratio; NA, not applicable; RR. relative risk.
a The HRs and RRs given for vitamin E, selenium, and selenium + vi tamin E groups are compared with the placebo group.
bNo. of participants that had more than 1 cancer for each gr01.1p are placebo (n=25), vitamin E (n=24), selenium (n=25), and selenium+ vitamin E (n=36).
c Excluding basal cell and squamous cell skin cancers.
d Based on self-report or reported use of diabetes medications of the glitazone class: excludes prevalent cases at randomization.
8
Not specifl8d as to whether an ischemic or hemorrhagic stroke.
!According to National Cancer Institute Common Toxicity Criteria.
HR
(99% CI)
1.02 (0.90-1.16)
1.16(0.76-1.78)
1.28 (0.82-2.00)
0.94 (0.76-1.16)
RR
(99%CI)
0.97 (0.85-1.1 1)
0.99 (0.89-1.10)
1.09 (0.37-3.19)
1.20 (0.75-1.90)
0.80 (0.37 - 1. 73)
1.00(0.87-1.15)
1.06 (0.82-1.37)
HR
(99% CI)
0.94 (0.77- 1.13)
0.93 (0.67-1 .30)
NA
0.95 (0.53- 1.69)
1.49 (0.52-4.28)
0.85 (0.551.32)
0.82 (0.60-1.13)
1 .49 (0.46-4.84)
0.78 (0.561.09)
1.08 (0. 78-1.51)
2009 American Medical Association. All rights reserved. (Reprinted) JAMA, Published online Dewnber 9, 2008 E9
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SELENIUM AND VITAMIN E FOR CANCER PREVENTION
limitations inherent in secondary analy-
ses, such as chance findings due to mul-
tiple testing, especially because the over-
all NPC sample size was relatively small
( 1312 men and women vs 29 133 men
in the ATBC study). Second, the fonnu-
lation (high-selenium yeast) given in the
NPC trial may have been more active
than the l-selenomethionine given in
SELECT (both trials gave an equivalent
selenium dose) . In designing SELECT,
we carefully evaluated the choice of l-
selenomethionine vs high-selenium yeast
(and other forrnulations),
20
and our ra-
tionale for selecting 1.-selenornethio-
nine included the following consider-
ations: selenomethionine was the major
component of apparently active high-
selenium yeast; evidence indicated sub-
stantial batch-to-batch variations in spe-
cific organoselenium compounds in
samples of NPC yeast, making it un-
likely that we could duplicate the sele-
nium yeast fonnulation used in the NPC
study; potential genotoxicity of highly ac-
tive inorganic selenium compounds,
such as selenite, made them potentially
unsuitable for long-term prevention; low-
ering (vs selenomethionine) of overall
body selenium stores with selenite, which
is neither absorbed nor retained well;
practical and safety concerns over newer
selenium compounds, such as mono-
methylated forms (eg, lacking availabil-
ity, investigational new drug certifica-
tion, and clinical data); and in vitro data
indicating that selenomethionine was ef-
fective in suppressing malignant and not
normal prostate cells.
15
Despite this careful rationale, it is im-
possible to know now whether sele-
nized yeast would have been more ac-
tive than l-selenomethionine was in
SELECT. Finally, the NPC trial was con-
ducted in men chosen for deficient lev-
els of selenium, finding that selenium was
most preventive in the men with the low-
est baseline selenium levels
9
; SELECT
men generally were replete in selenium
at baseline, with median serum sele-
nium levels of 135 ng/mL vs 113 ng/rnl
in NPC. The NPC cutpoint for the low-
est 2 tertiles was 121.6 units; 78% of
SELECT men were above this level. The
NPC trial found a nonsignificant in-
crease in overall cancer rate in its high-
est tertile (HR, 1.20; 95% CI, 0.77-1.86)
12
There are potential reasons why vita-
minE did not prevent prostate cancer in
SELECT. First, the high dose ( 400 lU/d)
of the a-tocopherol form of vitamin E in
SELECT may have been less effective
than a lower dose such as the 8-fold lower
50 mg/d (roughly equivalent to 50 IU/d)
that produced the earlier positive sec-
ondary findings in the A TBC study.
7
(The
vitamin E fommlation, synthetic all rac-
a -tocopheryl acetate, was the same in
Tabl e 5. Adverse Events Known to Be Associated With the Study Supplements
Placebo Vitamin E
(n = 8696) (n = 8737)
No. RR No. No.
Adverse Event of Men {99% Cl) of Men RR(99% Cl) of Men
Alopecia 206 1 [Reference] 220 1.06 (0.83- 1.36) 265
Dermatitis
Grades 1-2 516 1 [Reference] 591 1.14 (0.98-1.32) 605
Grades 3-4 8 1 [Reference) 12 1.49 (0.46-4.83) 14
Halitosis 427 1 [Reference) 493 1.15 (0.97 -1.36) 503
Nail changes 1035 1 [Reference) 1041 1.00 (0.90-1.1 1) 1087
Fatigue
Grades 1-2 586 1 [Reference] 604 1.03 (0.89-1.19) 645
Grades 3-4 24 1 [Reference) 29 1.20 (0. 59-2.45) 21
Nausea
Grades 1-2 203 1 [Reference) 191 0.94 (0. 72-1.21) 244
Grade 3 9 1 [Reference) 3 0.33 (0.06-1.85) 9
Abbreviations: Cl, confidence interval; RR, relative risk.
SELECT and the ATBC study.) A sec-
ondary analysis of the HOPE trial
23
found
that a relatively high dose of natural vi -
tamin E did not reduce prostate cancer
incidence. Achieving higher plasma or
tissue levels of a-tocopherol within the
physiological range, such as through a
50-mg/d supplement, may have some
prostate cancer (or other) preventive
effect such as cell proliferation or tu-
mor growth inhibition
24
Furthermore,
high pharmacological doses of a-
tocopherol may have an adverse effect on
cytochrome p450 enzyme and other
regulatory mechanisms
25
that a lower
dose would not have. It is also possible
(but not certain) that the known effect
of a -tocopherol in suppressing poten-
tially beneficial plasma "{-tocopherol lev-
els would have been less with the lower
than higher dose of a-t.ocopherot2 Nev-
ertheless, men taking vitamin E with the
highest baseline (and thus total) serum
vitamin E levels in the ATBC study had
the highest reduction in prostate and
lung cancer/
6
which supported our
choice of the higher dose. A higher dose
also was associated with potential ben-
efits such as reductions in aging-related
Alzheimer disease and macular degen-
eration.
Second, several studies have sug-
gested that vitamin E is more protective
against prostate cancer in smokers, and
Selenium Selenium + Vitamin E
(n = 8752) (n = 8703)
No.
RR {99% Cl) of Men RR{99% Cl)
1.28 (1.01-1.62)b 238 1.15 (0.91-1.47)
1.17 (1.00-1.35)b 554 1.07 (0.92-1 .25)
1.74 (0.56-5.44) 16 2 00 (0.66-6.09)
1.17 (0.99-1.38) 531 1 .24 (1.06-1.46)
1.04 (0.94-1.16) 1075 1 .04 (0.93-1.15)
1.09 (0.95-1.26) 612 1 .04 (0.90- 1.20)
0 87 (0.40-1.88) 20 083 (0.38- 1.81)
1.19 (0.941.52) 202 0.99 (0.77 1.28)
0.99 (0.30-3.34) 8 0.89 (0.25-3.10)
a The RRs given for vitamin E, selenium, and selenium + vitamin E groups are compared with the placebo group. Maximum grade experienced by a participant are given. AlOpecia,
halitosis. and nail changes were only defi ned for grades 1 and 2. National Cancer Institute Common Toxicity Criteria were used for alopecia, nail changes, fatigue, and nausea.
Halitosis and dermatitis were defined in the study protocol. Generally, grade 1 =mild, grade 2= moderate, grade 3= severe, and grade 4 =
bp< .OI .
E10 JAMA, Published online December 9, 2008 (Reprinted) 2009 American Medical Association. AU rights reserved.
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
less than 60% of SELECT men were cur-
rent or former smokers (whereas all men
in the ATBC study were smokers). For
example, observational analyses in a trial-
based cohort of the Prostate, lung, Co-
lo rectal, and Ovarian Cancer Screening
Trial (PLC0),
27
a trial of screening vs
standard health care routines, showed a
71% reduction in the incidence of ad-
vanced prostate cancer associated \'llith
supplemental vitamil1 E use in current
and recent smokers. A subgroup analy-
sis of current and former smokers in
SELECT, however, did not show a smok-
ing-related benefit (placebo, 4.6% [223/
4863] vs vitamin E alone, 4.8% [232/
4853]). As with selenium in the NPC
study, vitamin E effects on prostate can-
cer incidence in the A TBC study could
have been due to chance findings in sec-
ondary analyses.
Selenium was not associated \'llith sig-
nificant effects on cardiovascular events,
lung cancer, other cancers, or overall
mortality in SELECT. One safety con-
cern \'lli th selenium is a potential asso-
ciation with increased risk for type 2
diabetes mellitus, for which there are
mixed data from prior studies.
28

29
Are-
cent analysis of the NPC study popu-
lation showed a significant increase in
type 2 diabetes mellitus (by self-
reportand medical records) , largely lim-
ited to the top tertile of plasma sele-
nium levels at baseline.
30
In SELECT, a nonsignificant in-
crease in risk (RR, 1.07; P= .16) of dia-
betes mellitus compared with placebo
was observed in the selenium group but
not in the selenium + vitamin E group
(RR, 0.97; P=.62). Concerns about the
safety of vitamin E supplementation
arose during SELECT. One meta-
analysis31 found that vitamin Eat doses
of at least 400 IU/d increased all-cause
mortality, and another study3
2
found evi-
dence that vitamin E supplementation,
alone or in combination with other an-
tioxidants, may increase mortality. Nei-
ther sn.1dy is directly relevam to the doses
and poptllation studied in SELECT;
many studies included in these meta-
analyses were in patients \'llith serious dis-
ease, and the finding of increased mor-
tality was driven by studies using doses
SELENIUM AND VTTAMIN E FOR CANCER PREVENTION
far higher than 400 lUid. In more rel-
evant, placebo-controlled trials com-
pleted in healthy men and women, there
were no associations of vitamin E supple-
mentation \'llith increased risks of either
cardiovascular disease or overall mor-
tality. 33 SELECT results support the
safety of vitamin Eat 400 lU/d in healthy
men, because there were no increases in
either cardiovascular disease or total mor-
tality in the vitamin E groups.
The 35 533 randomized men of
SELECT were needed because of the ro-
bust statistical design accommodating 4
study groups with 5 p1imary compari-
sons; this large trial population made
SELECT the largest cancer chemopre-
vention trial ever conducted to our
knowledge. African American men have
among the highest prostate cancer risks
in the world, and SELECT had the high-
est participation of African American
men (13%) of any large-scale cancer che-
moprevention trial to date.
The statistical rigor of the trial was
matched by the rigor of its implementa-
tion. Features of this inlplementation in-
cluded the SELECT Workbench, a se-
cure Web site administered by the
SELECT statistical center and used by
study-site staff and investigators. The
SELECT Workbench was used to ac-
cess participant and site-specific re-
ports, the study protocol, and a detailed
study manual and to submit data using
Web-based forms. Form submission in-
cluded detailed edit checks and a track-
ing system to idenLify all expected forms.
Training and monitoring consisted of
semi-annual workshops, quality assur-
ance audits at least once every 3 years,
and mentoring by trained statistical cen-
ter staff and experienced clinical re-
search associates. SELECT also main-
tained a public Web site initially designed
to recruit participants and later used to
promote participant adherence and to
keep SELECT in the public's eye.
20
Potential limitations of SELECT in-
clude that it did not test different for-
mulations or doses of selenium and vi-
tamin E and that it did not definitively
assess results in subgroups of men who
may have responded differently than did
the overall population. Because of ac-
tive annual screening (eg, PSA in 85%;
Table 3) and early detection (eg, 99.4%
s tage Tl orT2; Table3),SELECT could
not assess effects in reducing advanced
or fatal prostate cancer, which recent data
suggest may be a potential benefit of vi-
tamin E and selenium.
18

27

34

36
SELECT
also could not assess intervention ef-
fects in a population deficient in vita-
min E, selenium, or both since our trial
population was well-nourished at base-
line, or in current smokers since they rep
resented only 7.5% of the SELECT popu-
lation, a substantial difference from the
ATBC study in predominantly heavy
smokers.
Cancer chemoprevention is an im-
portant approach for reducing cancer
burden.
37
Several randomized con-
trolled trials have demonstrated sig-
nificant cancer or premalignancy risk
r eductions in the breast , colon -
rectum, prostate, and stomach.JS.
44
Pros.
tate cancer is a particularly attractive
target for chemoprevention because of
its clinical ubiquity, substantial treat-
ment-associated morbidity, and step-
wise molecular pathogenesis. In the
large-scale PCPT, which was reported
2 years after SELECT was activated, fi-
nasteride produced a 25% relative re-
duction in the 7 -year period preva-
lence of prostate cancer ( vs placebo) ,
43
and recent data suggest that finaste-
ride reduces the risk of clinically sig-
nificant disease and may not induce
high-grade cancers despite initial con-
cerns to the contrary.
4
H
9
CONCLUSION
In conclusion, SELECT has definitively
demonstrated that selenium, vitamin E,
or selenium + vitamin E (at the tested
doses and formulations) did not pre-
vent prostate cancer in the generally
healthy, heterogeneous population of
men in SELECT. These data under-
score the prudence that is needed in con-
sidering recommendations to use agents
for the prevention or comrol of disease
in the absence of convincing clinical trial
results. These findings also compel the
medical research community to con-
tinue the search for new, effective agents
for prostate cancer prevention.
2009 American Medical Association. All rights reserved. (Reprinted) JAMA. Published online December 9, 2008 E11
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
SELENIUM AND VITAMIN E FOR CANCER PREVENTION
Published Online: December 9, 2008 (doi:1 0.1001/
jama. 2008.864)
Author Affiliations: Divisions of Cancer Medicine (Drs
Lippman and Karp) and Cancer Prevention and Popu-
lation Sciences (Drs Lippman and Cook), University of
Texas M.D. Anderson Cancer Center, Houston; Glick-
man Urological and Kidney Institute and Taussig Can-
cer Institute, Cleveland Clinic, Cleveland, Ohio (Or Klein);
Southwest Oncology Group Statistical Center, Seattle,
Washington (Dr Crowley and Mss P. Goodman. Hart-
line, Darke, and Arnold); Department of Pathology (Dr
Lucia) and Division of Urologic Oncology (Dr Crawford},
University of Colorado Health Sciences Center, Denver;
Departments of Urology (Dr Thompson) and Medicine/
Hematology and Medical Oncology (Dr Cottman), Uni-
versity of Texas Health Sciences Center, San Antonio; Di-
vision of Cancer Prevention (Drs Ford, Parnes. and Mi-
nasian) and Division of Cancer Epidemiology and Genetics
(Drs Albanes and Taylor), National Cancer Institute,
Bethesda, Maryland; Veterans Affairs Cooperative Stud-
ies Program and Massachusetts Veterans Epidemiology
Research and Information Center, Boston VA Healthcare
Center, Boston, Massachusetts (OrGaziano); Moores Can-
cer Center, La Jolla, California (Or Parsons); Upstate Caro-
lina CCOP, Spartanburg, South Carolina (Dr Bearden);
Division of Hematology and Oncology, Swedish Cancer
Institute. SeaWe. Washington (Dr G. Goodman); Alta-
mira Family Medicine, Rio Piedras. Puerto Rico (Dr Clau-
dio); London Regional Cancer Program, London Health
Sciences Center, London, Ontario, Canada (Or Winquist);
Department of Urologic Surgery, Duke University Medi-
cal Center, Durham. North Carolina (Or Walther); De-
partment of Urology, Mayo Clinic, Rochester, Minnesota
(Or Ueber); Departments ofEpidemioiOl,'Y (Or Krista!) and
Medicine and Cardiology (Or Probstfield), University of
Washington, Sea We; Division of Cancer Prevention and
Control Research, Jonsson Comprehensive Cancer Cen-
ter. University ofCalifomia, Los Angeles (Dr Ganz); Mail-
man School of Public Health, Columbia University, New
York, New York (Or Santella); Center for Clinical Epide-
miology and Evaluation, University of British Columbia,
Vancouver, Canada (Mr Jagpal); Chao Family Compre-
hensive Cancer Center. University of California at Irvine,
Orange (Dr Meyskens); and Division of Hematology and
Oncology, University of Michigan (Dr Baker), and South-
west Oncology Group (Drs Baker and Cottman), Ann Ar-
bor, Michigan.
Author Contributions: Drs Lippman and Klein had full
access to all of the data in the study and take respon-
sibility for the integrity of the data and the accuracy
of the data analysis. Both contributed equally to the
study.
Study concept and design: Lippman, Klein , P.
Goodman, Thompson. Ford, Parnes, Minasian,
Gaziano, Crawford, G. Goodman, Cook, Karp, Walther,
Lieber, Ganz. Santella, Albanes, Taylor, Probstfield,
Crowley, Meyskens, Cottman.
Acquisition of data: Klein, P. Goodman, Lucia, Hartline,
Parsons, Bearden. G. Goodman, Claudio, Winquist,
Cook. Lieber, Arnold, Jagpal, Crowley.
Analysis and interpretation of data: Lippman, Klein,
P. Goodman, Thompson, Ford, Parnes. Minasian,
Gaziano. Kri sta!, Darke. Arnold, Crowley, Baker.
Collman.
Drafting of the manuscript: Li ppman, Klei n,
P. Goodman, Thompson, Minasian, Darke.
Critical revision of the manuscript for important in-
tellectual content: Lippman, Klein, P. Goodman, Lucia,
Thompson, Ford, Parnes, Minasian, Gaziano, Hartline,
Parsons, Bearden, Crawford, G. Goodman, Claudio,
Winquist, Cook. Karp, Walther. Lieber, Krista!, Arnold,
Ganz, Santella, Albanes, Taylor. Probstfield. Jagpal,
Crowley, Meyskens, Baker, Collman.
Statistical analysis: P. Goodman, Darke, Arnold,
Crowley.
Obtained funding: Lippman, Cottman.
Administrative, technical, or material support:
Lippman, Klein, P. Goodman, Lucia, Thompson, Ford,
Minasian, Hartline, Bearden, Crawford. G. Goodman.
Claudio, Cook, Lieber, Ganz. Santella, Albanes, Taylor,
Probstfield, Meyskens.
Study supervision: Lippman, Klein, Thompson, Ford,
Minasian. Gaziano, Hartline, G. Goodman, Karp, Lieber.
Probstfield, Crowley, Baker, Cottman.
Financial Disclosures: Dr lucia reported serving as a con-
sultant for GlaxoSmithKiine and Veridex, and being a
member of the Advisory Board for GenProbe. Or Thomp-
son reported serving as a consultant torVeridex and Mis-
sion Pharmacal (with fees paid to University of Texas
Health Sciences Center, San Antonio). Dr Gaziano re-
ported receiving investigator-initiated research fund-
ing from Veroscience, Amgen, and BASF Corporation,
and research support in the form of study agents and
packaging from BASF Corporation, Wyeth Pharmaceu-
ticals, and DSM Nutritional Products Inc (formerly Roche
Vitamins); serving as a consultant or receiving hono-
raria from Bayer AG and Pfizer; and serving as an ex-
pert witness for Merck. Dr Meyskens reported being a
co-founder of Cancer Prevention Pharmaceuticals. No
other authors reported financial disclosures.
Funding/Support: This work was supported in part by
Public Health Service Cooperative Agreement grant
CA37429 awarded by the National Cancer Institute, Na-
tional Institutes of Health. Department of Health and
Human Services. and in part by the National Center for
Complementary and Alternative Medicine (National In-
stitutes of Health). Study agents and packaging were
provided by Perrigo Company (Allegan, Michigan), Sab-
insa Corporation (Piscataway, New Jersey), Tishcon Cor-
poration (Westbury, New York), and OSM Nutritional
Products Inc (Parsipanny, New Jersey).
Role of the Sponsor. The National Cancer Institute was
involved in the design and conduct of the study, in
the analysis and interpretation of the data, and in the
preparation, review, and approval of the manuscript.
Active SELECT Clinical Sites With ;;,:100 Participants
as of October23, 2008: San Diego, U ofCA: J. Kellogg
Parsons, principal investigator (PI) [1743 men); Up-
state Carolina CCOP: Jay Bearden Ill , PI (1201 men);
London Regional Cancer Program, London Health Sci-
ences Centre: Joseph l. Chin and Eric Winquist, Pis (981
men); University of Colorado: E. David Crawford, PI (964
men); Swedish Medical Ctr: Gary E. Goodman, PI (934
men); VAMC Jesse Brown: Thomas E. Lad, PI (749 men);
Harbor-UCLA: Rowan T. Chlebowski, PI (629 men); Le
Centre de Recherche: Yves Fradet, PI (628 men); Alta-
mira Family Med: Jaime Claudio, PI (610 men); Mayo,
Rochester: Michael M. Ueber, PI (606 men); Capital Re-
gion Prostate Centre: Gary Steinhoff, PI (543 men); Van-
couver Hospital: Mark FitzGerald, PI (423 men}; Rush
University Medical Center: Steven K. Rothschild, PI (385
men): MD Anderson Cancer Center: Elise D. Cook. PI
(381 men); VAMC San Juan: Luis Baez, PI (359 men);
SUNY Stony Brook: Iris A. Granek, PI (358); $her-
brooke University Hospital: Abdenour Nabid, PI (348
men); George Washington University: Richard J. Katz.
PI (342 men); William Beaumont Hospital: David A.
Decker, PI (321 men); Wilford Hall Medical Center: Kyle
J. Weld, PI (309 men); Cascadia Cancer Prevention at
St. Joseph Hospital: Frank E. James, PI (299 men); Day-
ton CCOP: Lawrence J. Litscher, PI (296 men); Grand
Rapids CCOP: Marianne K. Lange, PI (287 men); VAMC
Minneapolis: Timothy J. Wilt, PI (270 men); Carle Can-
cer Center CCOP: David l. Graham. PI (253 men); LOS
Hospital: Scott Chidester, PI (250 men); University of
Mississippi: Charles R. Pound, PI (238 men); Green-
ville CCOP: Jeffrey K. Giguere, PI (230 men); Metro-
Minnesota CCOP: Alice C. Shapiro, PI (229 men); VAMC
Cleveland: Donald R. Bodner, PI (227 men); Wichita
CCOP: Shaker R. Dakhil, PI (219 men); Arizona Can-
cer Center: Frederick R. Ahmann, PI (219 men); Marsh-
field Clinic Matthias Weiss, PI (215 men): University
of Iowa Hospital: Richard D. Williams, PI (207 men);
Baptist Hospital East: Keny Short, PI (202 men); Down-
state Medical Center: Richard J. Macchia, PI (197 men):
Kalamazoo CCOP: Raymond S. Lord Ill, PI (181 men);
Southern Nevada CCOP: John A. Ellerton. PI (173 men);
Sunnybrook Health Science Center: Laurence Klotz, MD,
PI (171 men); Missouri Baptist Medical Center: PaulK.
Schultz, PI (170 men); Geisinger Clinic Albert M. Ber-
nath, PI (165 men); VAMC Kansas City: Peter J. Van
Veldhuizen Jr., PI (163 men); Orocovis Med Ctr: Jose
S. Aponte, PI (163 men); Sutter Health Cancer Re-
search Group-Eastern Division: Vincent Caggiano, PI
(160 men); VAMC Washington, DC: Steven H. Kras-
now, PI (154 men): Bay Area CCOP: Norman R. Co-
hen, PI (153 men); Sentara Cancer Institute: Robert W.
Given, PI (152 men); VAMC Fargo: William K. Becker,
PI (151 men); Medical College of Wisconsin: Robert
F. Donnell, PI (149 men); VAMC Houston: Teresa G.
Hayes, PI (146 men); Baptist Regional Cancer fnsitute:
Neil Abramson, PI (136 men); Mount Sinai CCOP: Ro-
gerio C. Lilenbaum, PI (134 men); Methodist Hospi-
tals of Dallas: John V. Cox, PI (133 men); Miguel Sosa
Padilla: Miguel Sosa-Padilla, PI (133 men); Kaiser Perma-
nente: Nagendra R. Tirumali, PI (132 men); Duluth
CCOP: Steven A. Kuross, PI (131 men); Stormont- Vail
Health Care: Stanley J. Vogel, PI (130 men); Decatur
Memorial Hospital: James l. Wade Ill, PI (126 men);
VAMC Puget Sound: Daniel W. Lin, PI (124 men);
VAMC Boston: MaryT. Brophy, PI (122 men); Scott&
White CCOP: Scott Coffield, PI (119 men); Schiffler Can-
cer Center: Gregory S. Merrick, PI (116 men); Merit-
Care Hospital CCOP: Preston D. Steen, PI (115 men};
Gaston Memorial Hospital: Steven W. Yates. PI (114
men); VAMC Phoenix: James V. Felicetta. PI (113 men);
Lehigh Valley Hospital: Gregory R. Harper, PI (113 men);
Cancer Resource Ctr: Sushi! S. lacy, PI (112 men); Holy
Cross Hospital: Leonard J. Seigel, PI (112 men); Cleve-
land Clinic: Eric A. Klein, PI (111 men); Walter Reed
AMC: Rob Dean, PI (111 men); Kaiser Permanente-
GA: Joshua I. Barzilay. PI (110 men); Columbia River
CCOP: Keith S. Lanier, PI (110 men); Oregon Health &
Science University: Mark G. Garzotto,PI (1 10 men); H
Lee Moffitt Cancer Center: Julio M. Pow-Sang, PI (110
men); McGill University Health Center: Simon Tan-
guay. PI (11 0 men); Vanderbilt University: Michael S.
Cookson, PI (1 09 men); St Luke's Mountain State Tu-
mor Institute: Thomas M. Beck, PI (107 men); Wash-
ington University: Robert L. Grubb Ill, PI (107 men);
VAMC Southern Arizona: Maria C. Bishop, PI (1 06 men);
Andres Grillasca: Luis Baez, PI (106 men); VAMC Hines:
Nirmala Bhoopalam, PI (102 men): University of Okla-
homa: Daniel J. Culkin, Pl(1 02 men); Kaiser Permanente-
Oakland: Louis Fehrenbacher, PI (100 men); St Vin-
cent Hospital: Thomas J. Saphner, PI (100 men).
Intergroup Participants: Eastern Cooperative Oncol-
ogy Group: D. Karp (chief liaison): Cancer and Leu-
kemia Group 8: P. Walther (chief liaison); North Cen-
tral Cancer Treatment Group: M. Lieber (chief liaison);
Radiation Therapy Oncology Group: F. Khuri (chief
liaison); and Veterans Affairs Cooperative Studies Pro-
gram: M. Gaziano (chief liaison).
SELECT Steering Committee: Gary E. Goodman, MD,
Philip R. Taylor, MD, SeD, Powel H. Brown, MD. PhD,
Paul Godley, MD, PhD, Charles Bennett, MD, PhD.
Michael M. Lieber, MD, Lewis Musgrove. Ellen Rich-
mond, MS, RN, Alan R. Krista!, DrPH, Julia E. Ver-
trees, PharmD, Regina M. Santella, PhD, M. Scott Lu-
cia, MD, Demetrius Albanes, MD, Patricia A. Ganz,
MD, Jeffrey L. Probstfield, MD. Neil E. Fleshner, MD,
MPH, Isaac J. Powell, MD, T. J. Jagpal. CCRP, Wil-
liam R. Markesbery, MD, William Christen. SeD, Pa-
tricia A. Cassano, PhD, M. Peter Lance, MD, Carolyn
J. Hoban. DSc. Marjorie A. Godfrey, Abbie l. Brown,
Dana B. Sparks, MAT, Elaine Armstrong, MS, Frank
L. Meyskens Jr. MD, Cathy Tangen, OrPH, Garnet L.
Anderson, PhD, Amy Darke, MS, Katie Arnold, MS.
Karen Anderson, Monica Yee, Scott M. Lippman, MD,
Eric A. Klein, MD. Phyllis J. Goodman, MS. lan M.
Thompson, MD, Leslie G. Ford, MD, Howard L. Par-
nes, MD. J. Michael Gaziano, MD, MPH, Lori Mina
sian, MD, Jo Ann L. Hartli ne, MPH, J. Kellogg Par-
sons, MD, MHS, James D. Bearden, Il l, MD, Jaime
E1 2 JAMA, Published online December 9, 2008 (Reprinted) 2009 American Medical Association . AU rights reserved.
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
Claudio, MD, Elise D. Cook, MD, laurence H. Baker,
DO, John J. Crowley, PhD, Charles A. Coltman Jr. MD.
SELECT Committees and Subcommittees: Recruit-
ment and Adherence Committee: J. L. Probstfield
(chair); Minority and Medically Underserved Sub-
committee: E. D. Cook (chair); Health-related Qual-
ity of Life Committee: C. M. Moinpour and P. A. Ganz
(co-chairs); Pathology and Biomarkers Committee: M.
S. Lucia (chair); Molecular Epidemiology Commit
tee: R. M. Santella (chair); Diet and Nutrition Com-
mittee: A. R. Krista! (chair); Site Coordinators Com-
mittee: T. J. Jagpal (chair).
Disclaimer. Dr Gaziano, a contributing editor for lAMA,
was not involved in the editorial review of or decision
to publish this article.
Additional Contributions: We thank the 35 533 men
and many principal investigators and clinical research as-
sociates at our 427 clinical sites, whose participation in
SELECT has written an important chapter in the history
of cancer prevention. We also thank the many person
nel of the Southwest Oncology Group (the coordinat-
ing group of this Intergroup trial), whose tireless ef-
forts allowed SELECT to successfully complete the test
of its primary hypotheses. No compensation was re-
ceived.
REFERENCES
1. Jemal A, Siegel R, Ward E, et al. Cancer statistics,
2008. CA Cancer 1 C/in. 2008;58(2):7196.
2. Harlan SR. Cooperberg MR, Elkin EP, et al. Time
trends and characteristics of men choosing watchful
waiting for initial treatment of localized prostate can-
cer: results from CaPSURE. 1 Urol. 2003 ;1 70(5):
1804-1807.
3. Potosky AL, Legler J,Aibertsen PC, etal. Health out-
comes after prostatectomy or radiotherapy for prostate
cancer: results from the Prostate Cancer Outcomes Study.
1 Nat! Cancer lnst. 2000;92(19):1582-1592.
4. Stanford JL, Feng Z, Hamilton AS, et al. Urinary and
sexual function after radical prostatectomy for clini
cally localized prostate cancer: the Prostate Cancer Out-
comes Study. lAMA. 2000;283(3):354-360.
5. Cooperberg MR. Broering JM, Kantoff PW, Carroll
PR. Contemporary trends in low risk prostate cancer:
risk assessment and treatment. 1 Urol. 2007;178
(3 pt2):S14-S19.
6. Hoffman RM, Gilliland FD, Penson DF, Stone SN, Hunt
we, Potosky Al. Cross-sectional and longitudinal com-
parisons of health-related quality of lif e between pa-
tients with prostate carcinoma and matched controls.
Cancer. 2004;101 (9):2011-2019.
7. The Alpha-Tocopherol, Beta Carotene Cancer Pre-
vention Study Group. The effect of vi tamin E and beta
carotene on the incidence of lung cancer and other can-
cers in male smokers. N Eng! 1 Med. 1994;330(15):
10291035.
8. Clark LC, Combs GF Jr, Turnbull BW, et al; Nutri-
tional Prevention of Cancer Study Group. Effects of se
lenium supplementation for cancer prevention in pa-
tients with carcinoma of the skin: a randomized controlled
trial. lAMA. 1996;276(24):19571963.
9. Duffield-Lillico AJ. Dalkin Bl, Reid ME, et al; Nutri-
tional Prevention of Cancer Study Group. Selenium
supplementation, baseline plasma selenium status and
incidence of prostate cancer: an analysis of the com-
plete treatment period of the Nutritional Prevention of
Cancer Trial. BlU Int. 2003;91(7):608-612.
10. Heinonen OP, Albanes D. Virtamo J, et al. Pros-
tate cancer and supplementati on with alpha-
tocopherol and beta-carotene: incidence and mortality
in a controlled trial. 1 Nat! Cancer lnst. 1998;90(6):
440-446.
11. Blot WJ, Li JY, Taylor PR. et al. Nutrition interven-
tion trials in linxian, China: supplementation with spe
SELENIUM AND VITAMIN E FOR CANCER PREVENTION
cific vitamin/mineral combinations, cancer incidence, and
disease-specific mortality in the general population. 1 Nat!
Cancer lnst. 1993;85(18):1483-1492.
12. Fleshner N, Fair WR. Huryk R, Heston WD. Vita-
minE inhibits the high-fat diet promoted growth of es-
tablished human prostate LNCaP tumors in nude mice.
1 Urol. 1999;161(5):1651-1654.
13. lpC, Thompson HJ.ZhuZ. Ganther HE.Invitroand
in vivo studies of methylseleninic acid: evidence that a
monomethylated selenium metabolite is critical for can-
cer chemoprevention. Cancer Res. 2000;60(11 ):
28822886.
14. Jiang C. Wang Z, Ganther H,Lu J. Caspases as key
executors of methyl selenium-induced apoptosis (anoi-
kis) of DU-145 prostate cancer cells. Cancer Res. 2001;
61 (7):3062-3070.
15. Menter DG, Sabichi AL, Lippman SM. Selenium ef-
fects on prostate cell growth. Cancer Epidemio/ Bio-
markers Prev. 2000;9(11):1171-1182.
16. Redman C, ScottJA, Baines AT, etal. Inhibitory effect
of selenomethionine on the growth of three selected hu-
man tumor cell lines. Cancer Lett. 1998;125(1-2):
103-110.
17. Taylor PR, Albanes D. Selenium, vitamin E. and pros-
tate cancer-ready for prime ti me? 1 Nat/ Cancer lnst.
1998;90(16):1184-1185.
18. Yoshizawa K. Willett WC, Morris SJ. et al. Study of
prediagnostic selenium level in toenails and the risk of
advanced prostate cancer. J Natl Cancer Jnst. 1998;
90(16):1219-1224
19. Zhong W, Oberley TD. Redox-mediated effects of
selenium on apoptosis and cell cycle in the LNCaP hu-
man prostate cancer cell line. Cancer Res. 2001;
61 (19):7071 7078.
20. Lippman SM, Goodman PJ, Klein EA, et al. Design-
ing the Selenium and Vitamin E Cancer Prevention Trial
(SELEG). 1 Nat/ Cancer lnst. 2005;97(2}:94-102.
21. Current good manufacturing practice regulations,
21 CFR 210, 21 1.
22. Duffield-l illico AJ, Reid ME, Tumbull BW. etal. Base-
line characteristics and the effect of selenium supple-
mentation on cancer incidence in a randomized clinical
trial: a summary report of the Nutritional Prevention of
Cancer Trial. Cancer Epidemiol Biomarkers Prev. 2002;
11 (7):630639.
23. Lonn E,BoschJ, YusufS.etai;HOPEandHOPE-TOO
Trial Investigators. Effects of long-term vitamin E supple-
mentation on cardiovascular events and cancer: a ran-
domized controlled trial. lAMA. 2005;293(11):1338-
1347.
24. Venkateswaran V, Fleshner NE. Klotz LH. Modu-
lation of cell proliferation and cell cycle regulators by vi-
tamin E in human prostate carcinoma cell lines. 1 Urol.
2002;168(4 pt 1):1578-1582.
25. Traber MG. How much vitamin E? just enough! Am
1 C/in Nutr. 2006;84(5):959960.
26. Weinstein SJ, Wright ME, Pietinen P, et al. Serum
alpha-tocopherol and gamma-tocopherol in relation to
prostate cancer risk in a prospective study. 1 Nat/ Can-
cer lnst. 2005;97(5):396-399.
27. Kirsh VA, Hayes RB. Mayne ST. et al; PLCO Trial.
Supplemental and dietary vitamin E, beta-carotene, and
vitamin C intakes and prostate cancer risk. 1 Nat/ Can-
cer lnst. 2006;98(4):245254.
28. Bleys J, Navas-Acien A, Guallar E. Serum selenium
and diabetes in U.S. adults. Diabetes Care. 2007;
30(4):829834.
29. Rajpathak S, Rimm E, Morris JS, Hu F. Toenail se-
lenium and cardiovascular disease in men with diabetes.
1 Am Col/ Nutr. 2005;24(4):250-256.
30. Stranges S, Marshall JR, Natarajan R, et al. Effects
of long- term selenium supplementation on the inci-
dence of type 2 diabetes: a randomized trial. Ann In-
tern Med. 2007;147(4):217-223.
31 . Miller ER Ill, Pastor-Barriuso R, Dalal D, Riemersma
RA, Appel U, Guallar E. Meta-analysis: high-dosage vi-
tamin E supplementation may increase all -cause
mortality. Ann Intern Med. 2005;142(1):3746.
32. Bjelakovic G. Nikolova D, Gluud ll, Simonetti RG,
Gluud C. Mortality in randomized trials of antioxidant
supplements for primary and secondary prevention: sys-
tematic review and meta-analysis. lAMA. 2007;
297(8):842-857.
33. Sessa HD, Suring JE, Christen WG. et al. Vitamins
E and C in the prevention of cardiovascular disease in
men: the Physicians' Health Study II randomized con
trolled trial. lAMA. 2008;300(18):2123-2133.
34. Lee IM, Gaziano JM, Suring JE. Vitamin E in the pre-
vention of prostate cancer: where are we today? 1 Nat/
Cancer lnst. 2006;98(4):225 227
35. Li H, Stampfer MJ. Giovannucci El , et al. A pro
spective study of plasma selenium levels and prostate
cancer risk. 1 Nat/ Cancer tnst. 2004;96(9):696-703.
36. Taylor PR. Parnes HL, Lippman SM. Science peels
the onion of selenium effects on prostate carcinogenesis.
J Nat/ Cancer lnst. 2004;96(9):645-647.
37. Lippman SM. Lee JJ, Sabichi Al. Cancer chemo
prevention: progress and promise. 1 Nat/ Cancer lnst.
1998;90(20):1514-1 528.
38. Bertagnolli MM, Eagle CJ, Zauber AG, et al; APC
Study Investigators. Celecoxibforthe prevention of spo-
radic colorectal adenomas. N Eng/ 1 Med. 2006;
355(9):873-884.
39. Fisher B, Costantino JP, Wickerham DL, et al. Ta-
moxifen for prevention of breast cancer: report of the
National Surgical Adjuvant Breast and Bowel Project P-1
study. 1 Nat/ Cancer lnst. 1998;90(18):1371-1388.
40. Floss mann E, Rothwell PM; British Doctors Aspirin
Trial and the UK-TIA Aspirin Trial. Effect of aspirin on
long-term risk of colorectal cancer: consistent evi-
dence from randomised and observational studies.
Lancet. 2007;369(9573): 1603-1613.
41. Fukase K, Kato M, Kikuchi S, et al; Japan Gast Study
Group. Effect of eradication of Helicobacter pylori on
incidence of metachronous gastric carcinoma after en-
doscopic resection of early gastric cancer: an open-
l abel. randomised controlled t ri al. Lancet. 2008;
372(9636):392-397.
42. Meyskens FL. Mclaren CE. Pelot D. et al. Difluo-
romethylornithine plus sulindacforthe prevention of spo-
radic colorectal adenomas: a randomized placebo
controlled, double-blind trial. Cancer Prev Res. 2008;
1:9-11.
43. Thompson IM, Goodman PJ, Tangen CM, etal. The
influence of finasteride on the development of pros
tate cancer. N Eng/ 1 Med. 2003;349(3):215-224.
44. Vogel VG, CostantinoJP, Wickerham DL. etal; Na
tiona! SurgicalAdjwantBreastand Bowel Project(NSABP).
Effects of tamoxifen vs raJoxifene on the risk of devel-
oping invasive breast cancer and other disease outcomes:
the NSABP Study of Tamoxifen and Raloxifene (STAR)
P-2 trial. lAMA. 2006;295(23):2727 2741.
45. Scardino PT. The prevention of prostate cancer: the
dilemma continues. N Eng/ 1 Med. 2003;349(3):
297-299.
46. Logothetis CJ, Schellhammer PF. High-grade pros-
tate cancer and the Prostate Cancer Prevention Trial.
Cancer Prev Res. 2008;1 (3):151-152.
47. Lucia MS. Darke AK, Goodman PJ, et al. Patho-
logic characteristics of cancers detected in the Prostate
Cancer Prevention Trial: implications for prostate can
cer detection and chemoprevention. Cancer Prev Res.
2008; 1 (3): 167 173.
48. Lucia MS, Epstein Jl, Goodman PJ, et al. Finaste
ride and high-grade prostate cancer in the Prostate Can-
cer Prevention Trial. 1 Nat! Cancer tnst. 2007;99
(18):1375-1383.
49. Redman MW, Tangen CM, Goodman PJ, Lucia MS.
Collman CA Jr, Thompson IM. Finasteride does not in
crease the risk of high-grade prostate cancer: a bias-
adjusted modeling approach. Cancer Prev Res. 2008;
1(3):174-181.
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- ORIGINAL CONTIUBUTION JAMA-EXPRESS
Vitamins E and C in the Prevention
of Prostate and Total Cancer in Men
The Physicians' Health Study II Randomized Controlled Trial
J. i\lliehael Gaziano, MD, MPH
Robert J. Glynn, SeD
William G. Christen, SeD
Tobias Kurth, MD, SeD
Charlene Belanger, J.VIA
Jean MacFadyen, BA
Vadim Bubes, PhD
JoAim E. Manson, MD, DrPH
Howard D. Sesso, SeD, MPH
Julie E. Buring, SeD
I
N SOME OBSERVATIONAL STUDIES, IN-
take or blood levels of vitamins E
and C have been associated with re-
duced risk of certain cancers.
1
Ba-
sic research has provided pl ausible
mechanisms by which antioxidant mi-
cronutrients such as vitamin E and vi-
tamin C may delay various steps in car-
cinogenesis. ~ However, definitive proof
that vitamins E and C can reduce the risk
of overall or site-specific cancers must
rely on large-scale randomized trials.
A number of trials have addressed the
potential rol e of vitamins in the pre-
vention of cancer; however, the re-
sul ts from these trials have not been
consistent. Some
5
'
8
but not all
9
-
16
have
supported a role for various antioxi-
dants in the prevention of total or site-
specific cancers. The most compelling
data supporting a role of vitamin E in
the prevention of prostate cancer have
come from the Finnish ATBC (a-
Tocopherol, Beta Carotene) Cancer Pre-
vention Trial.
9
This trial was designed
See also related articles.
Context Many individuals take vitamins in the hopes of preventing chronic diseases
such as cancer, and vitamins E and C are among the most common individual supple-
ments. A large-scale randomized trial suggested t hat vitamin E may reduce risk of pros-
tate cancer; however, few trials have been powered to address this relationship. No pre-
vious t rial in men at usual risk has examined vitamin C alone in the prevention of cancer.
Objective To evaluate whether long-term vitami n E or C supplementation de-
creases ri sk of prostate and total cancer events among men.
Design, Setting, and Participants The Physicians' Health Study II is a random-
ized, double- blind, placebo-controlled factorial trial of vitamins E and C t hat began in
1997 and continued until its scheduled completion on August 31, 2007. A total of
14 641 male physicians in the United States ini tiall y aged 50 years or older, including
1307 men with a history of prior cancer at randomization, were enrolled.
Intervention Individual supplements of 400 IU of vitamin E every other day and
500 mg of vitami n C dai ly.
Main Outcome Measures Prostate and total cancer.
Results During a mean follow-up of 8.0 years, t here were 1008 confirmed incident
cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had
no effect on t he incidence of prostate cancer (active and placebo vitamin E groups, 9.1
and 9.5 events per 1000 person-years; hazard ratio [HR), 0.97; 95% confidence inter-
val [CI ). 0.85-1.09; P= .58) or t otal cancer (active and placebo vitamin E groups, 17.8
and 17.3 cases per 1000 person-years; HR, 1.04; 95% Cl, 0.95-1.13; P=.41)_ There
was also no signif icant effect of vitamin Con total cancer (active and placebo vitami n C
groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% Cl , 0.92-1 .10; P=.86)
or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000
person-years; HR, 1.02; 95% Cl, 0.90-1.15; P=.80). Neither vitamin E nor vitamin C
had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for
adherence and exclusion of t he first 4 or 6 years of follow-up did not alter the results.
Stratification by various cancer risk factors demonstrated no signif icant modification of
the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.
Conclusions In this large, long-term trial of male physicians, neither vitamin E norC supple-
mentation reduced t he risk of prostate or total cancer. These data provide no support for
the use of these supplements for the prevention of cancer in middle-aged and older men.
Trial Registration clinicaltrials.gov Identifier: NCT00270647
lAMA. 2009;301(1):(doi:10.1001/ jama.2008.862)
Author Affiliations: Divisions of Preventive Medicine
(Drs Gaziano, Gl ynn, Christen, Kurth, Bubes,
Manson, Sessa, and Buri ng and Mss Belanger and
MacFadyen), Aging (Drs Gazi ano, Kurth. Sesso.
and Buring), and Cardiovascular Di sease (Dr Gazi-
ano) , Department of Medicine, Brigham and Wom-
en's Hospital and Harvard Medi cal School, Boston,
Massachusetts; Massachuset ts Veterans Epi de-
miology Research and Information Center, VA Boston
www.jama.com
Healthcare System (Dr Gaziano), Boston; Depart
ment of Ambulatory Care and Prevention (Or Sur-
i ng), Harvard Medical School, Boston; and Depart-
ments of Epidemiology and Biostatistics (Drs Glynn,
Kurth, Manson, and Sesso), Harvard School of Public
Health, Boston.
Corresponding Author. J. Michael Gaziano, MD, MPH,
Brigham and Women's Hospital, 1620 Tremont St, Bos-
ton, MA 02120 (jmgaziano@partners.org).
2009 American Medical Association. All rights reserved. (Reprinted) JAMA, Published online Dewnber 9, 2008 E1
Downloaded from www.jama.com at Federal Trade Commission on December 10, 2008
VITAMINS E AND C AND CANCER PREVENTION IN MEN
to test the effect of vitamin E and beta
carotene on lung cancer risk among
current and past smokers. Although
there was no reduction in risk of lung
cancer with either agent, men as-
signed