ARTICLE IN PRESS

Progress in Biophysics and Molecular Biology 92 (2006) 119–131

www.elsevier.com/locate/pbiomolbio

Review

Adverse effects of ultraviolet radiation: A brief review

Richard P. Gallaghera,b,, Tim K. Leea,c
a
Cancer Control Research Program, BC Cancer Agency, 675 W. 10th Ave., Vancouver, BC, Canada V5Z 1L3
b
Department of Health Care and Epidemiology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
c
School of Computing Sciences, Simon Fraser University, Burnaby, BC, Canada
Available online 28 February 2006

Abstract

Solar ultraviolet radiation (UVR) has always been part of the environment of man. UVB is required for the conversion
of 7-deoxycholesterol to vitamin D, which is critically important in the maintenance of healthy bones and research is
making clear that it has other potential roles in maintenance of human health. Exposure to UVR, whether of solar or
artificial origin, also carries potential risks to human health. UVR is a known carcinogen and excessive exposure—at least
to solar radiation in sunlight—increases risk of cancer of the lip, basal cell, and squamous cell carcinoma of the skin and
cutaneous melanoma, particularly in fair skin populations. There is also evidence that solar UVR increases risk of several
diseases of the eye, including cortical cataract, some conjunctival neoplasms, and perhaps ocular melanoma. Solar UVR
may also be involved in autoimmune and viral diseases although more research is needed in these areas.
Artificial UVR from tanning beds, welding torches, and other sources, may contribute to the burden of disease from
UVR.
This brief review will assess the human evidence for adverse health effects from solar and artificial UVR and will attempt
to assign a degree of certainty to the major disease–exposure relationships based on the weight of available scientific
evidence.
r 2006 Elsevier Ltd. All rights reserved.

Keywords: Ultraviolet radiation; Sunlight; Cutaneous melanoma; Skin cancer; Cataract; Ocular melanoma

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
2. Scope of review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
3. Cutaneous diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
3.1. Skin cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
3.2. Cutaneous malignant melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
3.2.1. Solar UVR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
3.2.2. Artificial UVR exposure from sunbeds and sunlamps . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
3.2.3. Adverse effects of solar UV due to use of sunscreens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

Corresponding author. Cancer Control Research Program, BC Cancer Agency, 675 W. 10th Ave., Vancouver, BC, Canada V5Z 1L3.
Tel.: +1 604 675 8050.
E-mail address: rgallagher@bccancer.bc.ca (R.P. Gallagher).

0079-6107/$ - see front matter r 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.pbiomolbio.2006.02.011
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120 R.P. Gallagher, T.K. Lee / Progress in Biophysics and Molecular Biology 92 (2006) 119–131

3.3. Non-melanocytic skin cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

3.3.1. Solar UVR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
3.3.2. Artificial UV exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
3.4. Cancer of the lip . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
4. Diseases of the eye. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
4.1. Melanoma of the eye . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
4.1.1. Solar UVR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
4.1.2. Artificial UVR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
4.2. Cataracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
4.3. Age-related macular degeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
4.4. Pterygium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
4.5. Conjunctival neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
5. Other conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
6. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Further reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131

1. Introduction

Optical radiation within the electromagnetic spectrum includes ultraviolet radiation (UVR), visible light,
and infrared radiation. UVR, as used in this review, is defined as that radiation between 100 and 400
nanometres (nm) in length (WHO, 1994). It is characterized further according to wave length into ultraviolet
A (315–400 nm), B (280–315 nm) and C (100–280 nm).
The major source of UVR is solar radiation or sunlight, although exposure to artificial sources in the
workplace and tanning salons is becoming more important in terms of human health effects. Ultraviolet C
(UV-C), from the sun, is virtually completely screened out by the Earth’s atmosphere, and is thus a negligible
source of adverse human health effects. Ultraviolet B (UV-B) is responsible for erythema (sunburn), skin
cancer, and immunosuppression. However, solar UV-B is crucial in the synthesis of vitamin D, which some
recent studies suggest may potentially reduce risk of colon, prostate, and breast cancers. Ultraviolet A (UV-A)
is responsible for skin aging, and has more recently been implicated, along with UV-B, in the development of
skin cancers in animals and in immunosuppression in humans. Although the sun is the main source of UV-A
exposure, use of UV-A emitting lamps in sunbeds for recreational tanning has raised concern about artificial
sources of human exposure.

2. Scope of review

This review will focus only on the principal causes of morbidity and mortality attributable to UVR, namely
chronic diseases of the skin and eye. As the weight of scientific evidence for a causal relationship in each of the
disease–exposure associations to be covered differs somewhat, a judgement will be made at the end of each
section, similar to that used in the World Cancer Research Fund (1997) monograph on nutrition and cancer.
This assigns associations to one of four categories: (1) convincing evidence for a causal relationship, (2)
probable evidence, (3) possible evidence, and (4) insufficient evidence. ‘Convincing’ and ‘probable’ evidence
for a causal disease–exposure relationship should result in policy recommendations, while ‘possible’ and
‘insufficient’ evidence indicate the need for more research.
Cutaneous conditions to be reviewed include malignant melanoma, basal and squamous cell carcinoma
(SCC) of the skin, and cancer of the lip. Hereditary skin conditions such as xeroderma pigmentosum (XP), and
basal cell nevus syndrome, will be omitted. While skin cancers are common among XP patients (Kraemer et
al., 1987; Cleaver, 2005), the condition is very rare (1 in 40,000–1 in 150,000 among different ethnic groups),
and this ensures that it adds little to the population burden of disease from UVR.
This review will not cover the most common acute adverse skin effect resulting from solar (and sometimes
artificial UV) radiation: erythema (sunburn). The acute discomfort brought about by sunburn is obvious, and
the long-term effects are covered by the sections on melanoma and non-melanocytic skin cancer (NMSC).
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UVR is known to cause photoaging (Kligman et al., 1985; Malvy et al., 2000), and while this may be
considered an adverse effect, it is inextricably linked with aging in the normal course of human behaviour.
Thus, we will not consider photoaging in this review. Similarly, although solar UVR has been linked to the
formation of nevi, these are not, in the normal course of events, considered a disease entity, even though it is
likely that some proportion of cutaneous melanomas arise from nevi (Skender-Kalenas et al., 1995). The
review will not cover photodermatoses as many of these involve not only UVR, but also visible light.
Ocular diseases including uveal melanoma, cataract, macular degeneration, and pterygium and their
relationship to UVR will also be reviewed. However, acute photokeratitis will not be reviewed for reasons
analogous to those for acute skin erythema.

3. Cutaneous diseases

3.1. Skin cancer

The International Agency for Research on Cancer has noted that there is sufficient evidence from studies in
animals and in man to establish UVR as a human carcinogen (IARC, 1992). For the most part, this review will
focus on UVR as a single exposure without an attempt to separate the effects of UVA and UVB. This is
because most human evidence relates to reported sunlight exposure. When artificial sources of UVR are used
in animal studies, distinguishing the separate effects of UV-A and B is often possible; however, this has
remained difficult in human studies, most of which are retrospective and depend on subject recall. Animal
studies will not be quoted except where no alternative evidence is available.
This section of the review focuses initially on the relationship between UVR and the three major types of
skin cancer, cutaneous malignant melanoma (CMM), basal cell carcinoma (BCC), and SCC. In addition, the
relationship with cancer of the lip is discussed.

3.2. Cutaneous malignant melanoma

3.2.1. Solar UVR

CMM incidence has increased markedly over the past 25 years in Canada (Gallagher et al., 1990; Gaudette
and Gao, 1998), the US (Howe et al., 2001), Australia, and Northern Europe (Ferlay et al., 2001), and is a
significant public health problem in light skin populations. The major environmental risk factor is solar UV
exposure, and the principal modifying factor for the effect of this exposure is individual susceptibility as
indicated by pigmentation and sun-sensitivity.
Individuals with light skin, hair, and eye colour are consistently found to be at elevated risk of CMM in
virtually all epidemiologic studies of this tumour in the 1980s and 1990s (Elwood and Jopson, 1997).
Furthermore, propensity of the skin to burn rather than tan in the sun also consistently increases risk (Dubin
et al., 1986; Elwood et al., 1986; Holman and Armstrong, 1984a; Osterlind et al., 1988a, b;Gallagher et al.,
1986). Finally, the presence of either freckling (Elwood et al., 1984; Marrett et al., 1992) or acquired
melanocytic nevi (skin moles) substantially increases risk(Green et al., 1985; Holman and Armstrong, 1984b;
Marrett et al., 1992; Holly et al., 1987), and at least one study reported a synergistic effect of these two factors
(Osterlind et al., 1988a).
Solar UVR exposure is estimated to account for over 90% of melanomas in North America, and Australia
(Armstrong and Kricker, 1993), with similar figures for Northern Europe. Early descriptive studies suggested
an association between latitude of residence and melanoma incidence and mortality in Caucasian populations
(Lancaster, 1956; Elwood et al., 1974; Fears et al., 1976). The association, however, was not as strong as might
have been predicted if there was a simple, direct relationship between total UVR exposure and melanoma
incidence. This led investigators to hypothesize that the character and timing of exposure might be more
important than total lifetime exposure in inducing CMM (Elwood and Hislop, 1982; Holman et al., 1983;
Armstrong, 1988).
Over the past 25 years, a number of case-control and cohort studies have addressed the relationship of
CMM with solar UVR, many controlling for the effects of pigmentation and sun-sensitivity. Of the 57 studies
noted in the systematic review of Gandini et al. (2005), 34 evaluated a measure of ‘intermittent’ solar exposure,
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usually defined as outdoor recreational activities, sunbathing, or vacations in the sun. Most studies showed a
positive association between intermittent exposure and melanoma risk, and the relationship was statistically
significant in 18. The summary odds ratio for the highest exposure category was 1.61 (95%CI ¼ 1.31–1.99).
The summary odds ratio was higher for the estimate for the subgroup (number not given) of studies with
adequate control for phenotype (OR ¼ 2.35; 95%CI ¼ 1.78–3.09). ‘Chronic’ or more continuous solar
exposure (usually defined as occupational sun exposure) was assessed in 40 studies. The summary odds ratio
showed essentially no increased risk of melanoma (OR ¼ 0.95: 95%CI ¼ 0.87–1.04) in subjects. Total sun
exposure was studied in 13 investigations with a modestly increased summary odds ratio (OR ¼ 1.34;
95%CI ¼ 1.02–1.77). Of interest is the fact that the two studies (Grob et al. (1990) and Rodenas et al. (1996))
showing the highest risk with maximal total exposure were conducted in Mediterranean populations.
Overall, the results indicate that intermittent solar exposure is strongly associated with an increased risk of
melanoma, while occupational exposure does not appear to be associated with risk. Total or cumulative
exposure appears to be weakly related to risk, although this result must be treated with some caution. Most of
the studies cited that the meta-analyses were conducted in highly developed Western countries where indoor
work effectively limits the degree of cumulative exposure many people can accrue. Thus, a greater effect for
cumulative exposure might have been missed in many studies due to limited range of exposure. A previous
meta-analysis conducted on a smaller set of studies in 1997 showed essentially the same results (Elwood and
Jopson, 1997) as the 2005 analysis.
While recalled solar exposure indicates that the character of solar exposure is important in CMM, other
findings indicate that timing of exposure may also be important. Khlat et al. (1992), in a descriptive study,
demonstrated that migrants arriving in Australia after the age of 15 from low-sunlight areas, such as the UK,
had substantially lower mortality from CMM than those who arrived at a younger age. An Australian case-
control study also demonstrated a substantially reduced risk for melanoma in individuals coming to Australia
after age 9, (OR ¼ 0.34; 95%CI ¼ 0.16–0.72) by comparison with those who are native-born (Holman and
Armstrong, 1984b). A US study showed that early life spent in high-sunlight southern states conferred an
increased adult melanoma risk, even among subjects who later moved to low-sunlight states (Mack and
Floderus, 1991). Results of these investigations suggest that early life exposure may be important in relation to
later risk of CMM.
A significant concern with the data relating solar UV exposure to melanoma risk is that the increased
relative risks associated with exposure, even heavy exposure, have been relatively modest. This has been
largely attributed to the fact that it is difficult for most people to accurately recall their sun exposure history,
leading to substantial exposure misclassification. If the degree of misclassification is similar in cases and
controls, then the relative risks for a true disease–exposure relationship are likely to be biased toward the null.
There is some (but not extensive) data to suggest that this may be true—that the degree of accuracy with which
cancer patients and controls recall past sun exposure (or reports of sun exposure) is similar (Rosso et al., 2002;
Kricker et al., 2005). In addition, most studies did not attempt to assess solar exposure to the site of the
melanoma among cases (or corresponding anatomic site in control subjects). This could have had the effect of
further increasing the degree of exposure misclassification. Recently, several studies have suggested that there
may be at least two alternative etiologic pathways to melanoma (Whiteman et al., 2003; Purdue et al., 2005;
Siskind et al., 2005). These studies are potentially important as they suggest that the relationship of
susceptibility factors (skin colour, sun-sensitivity, nevus density, freckling) with melanoma, and perhaps even
the degree of solar exposure necessary for evolution of malignancy, may differ between the pathways. If this
proves to be the case, risk ratios associated with both susceptibility factors and solar exposure may actually
rise when it is possible to disaggregate etiologically distinct forms of the disease.
In summary, descriptive data indicates that melanoma rates are substantially higher among white
populations in high-sunlight areas (Parkin et al., 2002) than in similar populations in low-sunlight areas,
demonstrating an effect of solar UV at the population level. However, analytic studies indicate that character
and timing of exposure are important in accounting for risk at the individual level. Armstrong (1988) has
succinctly summarized the available information and has hypothesized that for a particular intermittent
pattern of exposure to solar UV, melanoma risk increases monotonically with increasing amount of exposure,
and for a given amount of exposure, risk increases monotonically as exposure becomes more intermittent.
There is convincing data for a causal relationship between solar UVR and cutaneous melanoma.
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3.2.2. Artificial UVR exposure from sunbeds and sunlamps

A number of studies evaluated risk of melanoma in sunlamp and sunbed users. Because most of the studies
conducted to date have had small numbers of exposed subjects, they have limited power to detect increases in
risk due to artificial UV. This has resulted in unstable risk ratios, with wide confidence intervals surrounding
point estimates. A recent meta-analysis was conducted in an attempt to summarize current knowledge
(Gallagher et al., 2005). Ten studies provided estimates of risk for being ‘ever exposed’ to sunbeds and
sunlamps. Where possible, risk ratios selected for inclusion in the analysis were those with adjustment for host
susceptibility and sun exposure. Compared to those with no exposure, those ever exposed had a statistically
significant increase in risk of CMM (OR ¼ 1.25; 95%CI ¼ 1.05–1.49). Compared with subjects having no
sunlamp or sunbed exposure, those with the ‘longest duration or highest frequency of exposure’ had a relative
risk of 1.69 (95%CI ¼ 1.32–2.18). The analysis suggests that the use of sunbeds and sunlamps does increase
risk of CMM. The results of the meta-analysis must be interpreted with caution, because there is likely to be at
least some residual confounding due to host factors. Furthermore, it is possible that individuals who use
sunbeds to tan may spend more time in the sun or engage in more concomitant sunbathing (Ramirez et al.,
2003; Hillhouse et al., 1996). If this exposure is not adequately controlled for in the analyses, it is possible that
the increased risk attributed to sunbed use might be a result of solar exposure. Finally, ‘recreational’ exposure
to artificial UV for tanning purposes prior to the early 1980s entailed substantial UV-B exposure, whereas
later (largely commercial) exposure was predominantly to UV-A. Thus, an analysis combining these exposures
could conceivably be aggregating qualitatively different exposures.
More research is necessary in this field to fully investigate the relationship between artificial UV and CMM.
There is evidence of a probable causal relationship between artificial UVR and cutaneous melanoma.

3.2.3. Adverse effects of solar UV due to use of sunscreens

It has been suggested that the advent of effective UV-B sunscreens in the 1960s, and their adoption for
common use shortly thereafter, may have inadvertently fuelled an increase in CMM incidence (Garland et al.,
1993). These authors propose that light-skinned individuals might expose themselves to the sun for much longer
periods than previously possible, because the onset of erythema is delayed by sunscreen use, making possible
substantially more UV-A exposure. Evidence from the basic sciences for the effect of UV-A in melanogenesis is
conflicting. Studies using the Xiphophorus fish model have demonstrated that UV-A radiation can induce
malignant melanoma in this species (Setlow et al., 1993; Setlow and Woodhead, 1994). However, there is
concern that this disease may not be analogous to human melanoma. Work with the HGF/SF mouse model
suggests that only UVB, and not UVA, is effective in inducing melanoma (deFabo et al., 2004).
A randomized trial conducted by Autier et al. (1999) tested the hypothesis that use of high sun-protection
factor (SPF) sunscreens encourages longer exposure. Study subjects were randomized to unlabelled SPF 10 or
SPF 30 sunscreen prior to vacation with instruction to use the sunscreen as needed, and record time in the sun.
Both groups used similar amounts of sunscreen, recorded similar sunburn patterns, and similar mean vacation
days, but subjects randomized to the SPF 30 compound spent significantly more time in the sun each day than
those randomized to the lower SPF sunscreen. However, again the evidence is conflicting, as not all studies have
demonstrated prolonged sun exposure in those using high-SPF sunscreens (Dupay et al., 2005). It should be
noted that the increase in incidence of CMM began prior to the advent of sunscreens (Osterlind and Jensen,
1986), and that recent data suggest that age-standardized melanoma incidence rates are levelling off and
perhaps beginning to decline (Marrett et al., 2001) in young people. This trend is happening in the face of
increasing popularity of very-high-SPF sunscreens which should be allowing greater UV-A exposure than ever.
More research is likely to focus on the role of UV-A versus UV-B, and on the effect of sunscreen use in the
genesis of cutaneous melanoma in the next few years.

3.3. Non-melanocytic skin cancer

3.3.1. Solar UVR

Descriptive data collected in the US in 1977–78 on the relationship between ambient solar UVR and the two
major forms of NMSC; BCC and SCC, indicated an incidence gradient from north to south (Scotto et al.,
1983). This gradient reinforced the clinical impression that skin cancers were directly related to cumulative
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solar UV exposure. However, results from recent analytic studies suggest that the relationship of SCC and
BCC to UVR is as complex as that seen for CMM. These investigations were designed specifically to separate
the contributions of ‘intermittent’, ‘chronic’, and ‘total’ solar exposure to BCC and SCC.
BCC: Results from the Australian study of Kricker et al. (1995) indicated an elevated risk of BCC with
increasing exposure to recreational UVR prior to age 20 (OR ¼ 3.86; 95%CI ¼ 1.93–7.75). A similar
increased risk (OR ¼ 2.6; 95%CI ¼ 1.1–6.5) with exposure prior to age 20 is seen in the Canadian study of
Gallagher et al. (1995a). No increase is seen with exposure in adult life in either study. The southern European
study of Rosso et al. (1996) also detected an increasing risk of BCC with increasing childhood (OR ¼ 1.43;
95%CI ¼ 1.09–1.89) and lifetime beach recreational exposure (OR ¼ 1.58; 95%CI ¼ 1.27–1.96). Similar
elevated risks were seen with lifetime holiday exposure (OR ¼ 1.47; 95%CI ¼ 1.18–1.83). Two further studies
of BCC in Italian populations confirmed the elevated risk of BCC with beach or beach vacation exposure prior
to age 20 (Naldi et al., 2000; Corona et al., 2001).
SCC: For SCC, the weight of evidence appears to suggest that risk is related to measures of ‘chronic’
(occupational) or total exposure. In the study of Gallagher et al. (1995b), an elevated risk is seen with
occupational exposure in the 10 years prior to diagnosis (OR ¼ 4.0; 95%CI ¼ 1.2–13.1). The South European
study (Rosso et al., 1996) demonstrates a trend to increased risk with lifetime occupational exposure
(OR ¼ 1.6; 95%CI ¼ 0.93–2.75). The Australian studies (English et al., 1998) indicate an increase in risk with
longer-term total sun exposure, although the point estimate dropped somewhat in the highest exposure
category.
It appears that CMM and BCC share a number of similarities in their relationships with solar UVR. Both
appear much more strongly related to measures of intermittent UV exposure, particularly in early life, than to
measures of cumulative lifetime exposure. SCC appears to be different in that it owes more to high levels of
cumulative sun exposure than to intermittent exposure. In addition, there is as yet little evidence that reported
sun exposure in childhood or youth is important in SCC.
There is convincing evidence for a causal relationship between solar UVR and both BCC and SCC.

3.3.2. Artificial UV exposure

There have been few studies specifically addressing the potential relationship between risk of NMSC. An
early study (Aubrey and MacGibbon, 1985) found a substantial elevated risk of SCC with use of sunlamps,
but the risk estimate was based on small numbers of subjects. A recent American study (Karagas et al., 2002)
showed an increased risk of SCC with use of tanning lamps (OR ¼ 2.5; 95%CI ¼ 1.7–3.8) and a more modest
risk for BCC (OR ¼ 1.5; 95%CI ¼ 1.1–2.1) Two other studies showed no association with sunlamps or
tanning beds (Bajdik et al., 1996; Rosso et al., 1999), but both studies had limited power due to low exposure
prevalence. The lack of data on this issue is of concern, as sunbed use appears to be increasing in the young.
Well-conducted analytic studies with quantitative exposure data and good control for host susceptibility
factors and concomitant sun exposure are urgently needed to clarify risk.
There is evidence of a possible causal relationship between artificial UVR and NMSC.

3.4. Cancer of the lip

Cancer of the lip is rare in Canada, the US, and Europe, and comprises only about 0.1% of cancers in
females and 0.4% in males in 2001 (National Cancer Institute of Canada, 2005). Descriptive studies show that
lip cancer is more common in males than females, and that incidence rates are higher in light- than dark-
skinned populations living in the same geographic area (Parkin et al., 1997). Evaluation of mortality and
incidence data from Australia indicate that rates of lip cancer are lower in migrants from low-sunlight areas
than they are in native-born Australians (Armstrong et al., 1983; McCredie and Coates, 1989). This finding is
suggestive of the pattern seen in malignant melanoma in Australia (Khlat et al., 1992) and could indicate the
importance of sun exposure in youth for lip cancer. However, it is more likely due to accrual of higher
cumulative sun exposure levels in native-born Australians than in migrants.
Several studies have indicated that outdoor workers such as farmers (Gallagher et al., 1984; Olsen and
Jensen, 1987; Wiklund and Dich, 1995) and fishermen (Spitzer et al., 1975) have elevated risks for lip cancer. A
case-control study conducted in Los Angeles to evaluate risk factors associated with sex differences in lip
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cancer incidence showed higher risk in those with fair complexion and in smokers (Pogoda and Preston-
Martin, 1996). Risk was strongly related to lifetime sun exposure and to annual time spent outdoors. Among
women with high lifetime sun exposure, risk was twice as high in women using lip protection (mostly lipstick)
once per day or less, than those using it at least twice per day. These findings suggest much of the overall lower
incidence rate in women as compared to men, may be attributed to the use of lip protection by women.
There is sufficient evidence for a causal relationship between solar UVR and cancer of the lip.

4. Diseases of the eye

4.1. Melanoma of the eye

4.1.1. Solar UVR

Ocular melanoma is a rare condition with an incidence rate in North America, Europe, and Australia of
between 6 and 10 per million population (Parkin et al., 2002). Descriptive data show higher incidence rates in
white populations than in African and Asian populations in the same fashion as is seen in cutaneous
melanoma. The rarity of this cancer has meant that few studies have been conducted.
Data from case-control studies (Gallagher et al., 1985; Tucker et al., 1985; Holly et al., 1990; Seddon et al.,
1990; Vajdic et al., 2001) indicated that subjects with blue or grey eyes, and light hair and skin colour are at
elevated risk of ocular melanoma. Tucker et al. (1985) found an elevated risk of ocular melanoma in subjects
born in the southern US (and thus perhaps exposed to higher levels of UVR in childhood) by comparison with
those born in the north. Elevated odds ratios were also seen for subjects who reported gardening outdoors, but
similar associations were not seen with other outdoor activities. No elevated risks for solar exposure were seen
in the study of Holly et al. (1990). Seddon et al. (1990) compared 197 patients with ocular melanoma with 385
controls recruited through random digit dialling and found an elevated risk of ocular melanoma in subjects
with 5 or more years residence in the Southern US. An extended analysis comparing 387 cases with 800 sibling
controls showed a gradient of risk with cumulative intense sun exposure, with a 2-fold increased risk in the
highest exposure group. Perhaps the best evidence for an association between ocular melanoma and sun
exposure comes from Australia. A national case-control study of ocular melanoma cases diagnosed between
1996 and mid-1998 demonstrated an increase in risk of the cancer with increasing quartile of sun exposure
prior to age 40 (RR in highest quartile ¼ 1.8; 95%CI ¼ 1.1–2.8), after control for phenotypic susceptibility
factors (Vajdic et al., 2002).

4.1.2. Artificial UVR

Three studies on sunlamp and sunbed use (Tucker et al., 1985; Holly et al., 1990; Seddon et al., 1990) have
shown at least one measure of exposure to be related to increased risk of ocular melanoma, although only two
of these risk estimates are statistically significant. The exposure prevalence was small and these results must be
interpreted cautiously.
A recent meta-analysis (Shah et al., 2005) which utilized exposure to welding as a surrogate for intermittent
UV exposure detected a significantly elevated risk with exposure (OR ¼ 2.05; 95%CI ¼ 1.20–3.51). However,
outdoor leisure exposure, as reported by study subjects, was not found to be a significant risk factor. Chronic
occupational ultraviolet exposure was of borderline significance (OR ¼ 1.37; 95%CI ¼ 0.96–1.96).
Although the data are less convincing than that seen with cutaneous melanoma, the phenotype susceptibility
profiles of both diseases are similar, and in spite of the difficulties in studying this rare disease retrospectively,
most studies have shown a relationship with at least one measure of solar or artificial UV exposure.
There is evidence of a probable relationship between ocular melanoma and UVR, either solar or artificial

4.2. Cataracts

Cataract is a clouding of the lens of the eye or its transparent membrane which obstructs light entry and
impairs vision. Cataract constitute one of the most common causes of vision impairment worldwide, and the
morbidity from the disease falls most heavily on those in undeveloped countries. Bachem (1956) showed
experimentally that cataracts in small animals can be induced in the laboratory using UVR. A number of
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case-control and cohort studies (Taylor et al., 1988; Cruickshanks et al., 1992; West et al., 1998; McCarty
et al., 2000; Delcourt et al., 2000) have shown increased risk of cataract formation with high solar exposure,
although the risk appears to be restricted to cortical cataracts. There appears to be no convincing evidence
that UVR, either solar or artificial, is causally related to nuclear or subcapsular cataract formation. A
systematic review of the human evidence for a causal relationship between UV exposure and cataracts was
conducted by McCarty and Taylor (2002). Of the 22 epidemiologic studies, 15 demonstrated a significant
association between UV exposure and (primarily) cortical cataract.
There is convincing evidence of a causal relationship between UVR and the formation of cortical cataract.

4.3. Age-related macular degeneration

Age-related macular degeneration (AMD) is a disease in which deposits (drusen) accumulate slowly over
time in the part of the retina of most importance to visual acuity causing impairment. A less common rapidly
progressing form of macular degeneration also exists and is characterized by bleeding and fluid leakage under
the retina. AMD is the most common cause of blindness in older individuals in developed countries (Delcourt
et al., 2001). There is some evidence that the disease is more common in subjects with light iris colour (Mitchell
et al., 1998), although not all studies report this association (West et al., 1989; Wang et al., 2003). Data from
one investigation indicated that the condition might be more common in those with very fair skin, although
the elevated risk is modest (Wang et al., 2003).
Studies of sunlight exposure have produced mixed results. Findings from the Beaver Dam Eye Study
suggest that exposure to UVR might increase risk of AMD (Cruickshanks et al., 1993; Tomany et al., 2004). A
French study, however, reviewed residence history and after adjustment for ambient solar radiation at each
area found no association between AMD and solar UV, although the study had fairly low power to detect an
association (Delcourt et al., 2001). Other investigations have also failed to confirm an association with UV
light (Wang et al., 2003; Hyman et al., 1983; West et al., 1989; Eye Disease Case-Control Study Group, 1992).
There is some evidence that blue light (400–500 nm in the visible spectrum) might be related to AMD. These
wavelengths produce the most photochemical damage to the retinal pigment epithelium in animal studies
(Ham et al., 1984), suggesting biological plausibility for an association with AMD. Furthermore, the
Maryland Watermen study (West et al., 1989), although showing no association with UVR, demonstrated an
increased risk of AMD in those with the highest exposure to visible light in the 20 years prior to the study.
Blue light, of course, is a component of visible sunlight.
There is insufficient evidence to determine whether UVR (solar or artificial) is causally related to AMD.
More study is needed on both UV and visible light to clarify this issue.

4.4. Pterygium

Pterygium occurs most commonly in very sunny climates and there is evidence that it is related to solar UV
exposure (Threllfall and English, 1999; Taylor et al., 1989; Moran and Hollows, 1984). At present, it is not
clear how UV exposure induces pterygium, but theories implicate extracellular matrix remodelling,
stimulation of the action of cytokines, and immunological mechanisms (Di Girolamo et al., 2004).
There is evidence for a probable causal relationship between UVR and pteryium.

4.5. Conjunctival neoplasms

Squamous intraepithelial neoplasms of the conjuctiva or cornea have been shown to be more common in
those with fair skin (Basti and Macsai, 2003; Lee and Hirst, 1995). A number of studies have shown a
relationship between UV exposure and this tumour (Rosenthal et al., 1988; Erie et al., 1986; Lee et al., 1994;
Newton, 1996), although the etiology probably also includes cigarette smoking and perhaps human papilloma
virus involvement (Scott et al., 2002).
There is evidence for a probable relationship with solar UVR, although one or more co-factors may be
necessary.
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5. Other conditions

Adverse effects from a number of autoimmune diseases appear to be potentiated by sunlight exposure. UV
exposure may play a role in the pathogenesis of dermatomyositis, an inflammatory disease, characterized by
skin rash followed by progressive muscle weakness. Patients in one study demonstrated a reduced minimal
erythemal dose threshold and increased photosensitivity by comparison with control patients (Dourmishev et
al., 2004). The study also showed a similar result for lupus erythematosis patients. Other studies have shown
that use of sunscreens by patients with systemic lupus erythematosis (SLE) reduces renal involvement,
thrombocytopenia, and hospitalizations (Vila et al., 1999), suggesting that attenuating UV-B exposure reduces
the severity of the disease. A study carried out in Finland in which SLE patients were examined in the winter,
spring, and summer by a rheumatologist and a dermatologist (Hasan et al., 2004) demonstrated higher SLE
activity scores in the spring and summer than in winter indicating that SLE may be activated by sun exposure.
On the other hand, there has also been work suggesting that long-wave UV (UV-A-1) exposure may reduce
constitutional symptoms, and joint pain in SLE patients (McGrath, 1999). More research is needed on the
relationship of UVR and autoimmune diseases
The course of virus-associated chronic diseases may also be affected by sunlight. UV-B activates a number
of viruses, including human papilloma virus (Chadonnet et al., 1989), perhaps due to its known suppressive
action against cellular immune function (Hersey et al., 1983). A recent study in the Netherlands demonstrated
twice as many premalignant and malignant changes in Pap smears taken in the summer than winter
(Hrushesky et al., 2005). Monthly sunlight fluency was positively correlated with monthly rates of carcinoma
in-situ, cervical epithelial dysplasia, and HPV infection. No association of sunlight with pregnancy rates—
proposed by the study authors as a surrogate indicator of sexual activity—was seen, suggesting that the
association was not due to increased sexual activity in sunnier months.
Descriptive data have been used to suggest that sunlight exposure may be important in the etiology of non-
Hodgkin lymphoma (NHL). First, the increase in incidence of NHL roughly parallels the increases seen for
CMM and NMSC (Adami et al., 1995; Cartwright et al., 1994) This suggests that the factors known to be
responsible for the increases in skin cancers may also be involved in NHL. Also, there appear to be parallel
gradients of risk for NHL, CMM, and SCC with proximity to the equator (Bentham, 1996; Swerdlow and Dos
Santos Silva, 1994; McMichael and Giles, 1996). Evidence from carefully conducted case-control studies to
date, however, does not support a positive relationship. A recently reported study in Australia found an inverse
exposure–response relationship (OR highest quartile ¼ 0.65; 95%CI ¼ 0.46–0.91) between total sun exposure
and NHL (Hughes et al., 2004). Similar results were seen in a Scandinavian study (Smedby et al., 2005).

6. Conclusions

Ultraviolet radiation, in solar or artificial form, is responsible for a substantial burden of human skin and
eye diseases, and likely plays a role in potentiating several autoimmune diseases, and activating some viral
diseases. Evidence of its adverse effect is strongest for cutaneous melanoma, non-melanocytic skin cancer, and
cancer of the lip. There is also fairly strong evidence that it is directly involved in squamous epithelial
neoplasms of the conjuntiva.
The evidence for its adverse effect on the eye is strongest for cortical cataract and pterygium and slightly
weaker for ocular melanoma. The evidence is insufficient to determine whether age-related macular
degeneration is related to UV exposure. More research on this putative association is urgently needed, as the
aging of populations in developed countries ensures that this disease will assume greater importance in the
near future. The suggestion that blue-light exposure (400–500 nm) may be related to AMD should also be
explored.

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Further reading

Aitken, J., Welch, J., Duffy, D., Milligan, A., et al., 1999. CDKN2A variants in a population-based sample of Queensland families with
melanoma. J. Natl. Cancer Inst. 91, 446–452.
Elwood, J.M., Gallagher, R.P., Hill, G.B., et al., 1985. Cutaneous malignant melanoma in relation to intermittent and constant sun
exposure: the Western Canada Melanoma Study. Int. J. Cancer 35, 427–433.
Kefford, R., Newton-Bishop, J., Bergman, W., et al., 1999. Counselling and DNA testing for individuals perceived to be genetically
predisposed to melanoma: a consensus statement of the Melanoma Genetics Consortium. J. Clin. Oncol. 17, 3245–3251.