WHAT IS CANCER AND HOW DOES IT AFFECT THE HUMAN CONDITION ?

Karobi Moitra (Ph.D)

NCI Frederick , NIH Cancer Inflammation Program Human Genetics Section Frederick MD.

Is cancer a single disease or a group of diseases ?

Cancer is a group of related diseases which are characterized by uncontrolled cellular growth and division

Earliest signs of cancer : 3000 BC

Origin of the word Cancer

The origin of the word cancer is credited to the Greek physician Hippocrates (460370 B.C.), considered the "Father of Medicine." Hippocrates used the terms carcinos and carcinoma to describe non-ulcer forming and ulcer-forming tumors. In Greek, these words refer to a crab, most likely applied to the disease because the finger-like spreading projections from a cancer called to mind the shape of a crab. The Roman physician, Celsus (28-50 B.C.), later translated the Greek term into cancer, the Latin word for crab. Galen (130-200 A.D.), another Roman physician, used the word oncos (Greek for swelling) to describe tumors. Galen's term is now used as a part of the name for cancer specialists -- oncologists.

Cancer is associated with abnormal cellular proliferation

Cells divide when they should not divide and they lack the normal control systems to shut off unwanted cell division

Loss of Normal Growth Control

Normal cell division
Cell Suicide or Apoptosis Cell damage no repair

Cancer cell division

First mutation

Second mutation

Third Fourth or mutation later mutation Uncontrolled growth

In most cases to form a contiguous cell mass called a tumor

Example of Normal Growth

Dead cells shed from outer surface

Epidermis

Cell migration

Dividing cells in basal layer

Dermis

Each time one of these basal cells divides, it produces two cells. One remains in the basal layer and retains the capacity to divide. The other migrates out of the basal layer and loses the capacity to divide. The number of dividing cells in the basal layer, therefore, stays the same.

The Beginning of Cancerous Growth

During the development of skin cancer, the normal balance between cell division and cell loss is disrupted. The basal cells now divide faster than is needed to replenish the cells being shed from the surface of the skin. Each time one of these basal cells divides, the two newly formed cells will often retain the capacity to divide, thereby leading to an increase in the total number of dividing cells.

Cell death = Cell growth

Cell death < Cell growth

Tumors (Neoplasms)

Underlying tissue
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This gradual increase in the number of dividing cells creates a growing mass of tissue called a tumor or neoplasm.

Melanoma
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Types of cancer / precancerous subtypes:

According to growth type: Neoplasia - growth of cells to form a new structure eg: a tumor Hyperplasia - excessive no. of cells. Dysplasia - loss of normal arrangement of tissue (precancerous) Carcinoma-in-situ - uncontrolled growth of cells that remains at the same place (non-invasive). Invasive carcinoma - can invade surrounding tissue and also undergo metastasis.

Hyperplasia
Excessive growth

Normal

Hyperplasia

Dysplasia
Excessive growth Loss of cellular structure & tissue arrangement

Normal

Hyperplasia

Mild dysplasia
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Normal to Invasive

Excessive growth

Loss of cellular structure & tissue arrangement

Excessive growth in place

Invades

Normal

Hyperplasia

Mild dysplasia

Carcinoma in situ (severe dysplasia)

Cancer (invasive)

Types of cancer / precancerous subtypes:

According to growth type: Neoplasia - growth of cells to form a new structure eg: a tumor Hyperplasia - excessive no. of cells. Dysplasia - loss of normal arrangement of tissue (precancerous) Carcinoma-in-situ - uncontrolled growth of cells that remains at the same place (non-invasive). Invasive carcinoma - can invade surrounding tissue and also undergo metastasis.

According to tissue type affected : Carcinoma - tumors made up of principally epithelial cells (cells that line inner and outer surfaces). eg: cervical and skin cancers. Sarcoma made up principally of connective tissue cells (cartilage, bone etc.) eg: osteosarcoma.

Leukemia - Neoplastic growth of leucocytes (WBC) . Lymphoma - excessive production of lymphocytes by lymph nodes and spleen. eg: Hodgkins disease.

Different Kinds of Cancer

Some common carcinomas:

Lung Breast (women)

Leukemias:
Bloodstream

Lymphomas:
Lymph nodes

Colon Bladder Prostate (men)

Some common sarcomas:

Fat Bone Muscle
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According to tissue type affected : Carcinoma - tumors made up of principally epithelial cells (cells that line inner and outer surfaces). eg: cervical and skin cancers. Sarcoma made up principally of connective tissue cells (cartilage, bone etc.) eg: osteosarcoma.

Leukemia - Neoplastic growth of leucocytes (WBC) . Lymphoma - excessive production of lymphocytes by lymph nodes and spleen. eg: Hodgkins disease.

According to metastasis (invading capacity)

Benign tumor - these tumors have restricted growth and tend to remain localized. eg: wart.

Malignant tumor - these tumors do not remain localized but invade other tissue and give rise to secondary tumors in other parts of the body (metastasis).

Malignant versus Benign Tumors

Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites

Time
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Invasion and Metastasis

1 Cancer cells invade surrounding tissues and blood vessels 2 Cancer cells are transported by the circulatory system to distant sites 3 Cancer cells reinvade and grow at new location

Different kinds of cancer

According to growth type:

Neoplasia - growth of cells to form a new structure eg: a tumor Hyperplasia - excessive no. of cells. Dysplasia - loss of normal arrangement of tissue (precancerous) Carcinoma-in-situ - uncontrolled growth of cells that remains at the same place (non-invasive). Invasive carcinoma - can invade surrounding tissue and also undergo metastasis.

According to tissue type affected :

Carcinoma - tumors made up of principally epithelial cells (cells that line inner and outer surfaces). eg: cervical and skin cancers. Sarcoma made up principally of connective tissue cells (cartilage, bone etc.) eg: osteosarcoma.

According to metastasis (invading capacity)

Benign tumor - these tumors have restricted growth and tend to remain localized. eg: wart.

Leukemia - Neoplastic growth of leucocytes (WBC) . Lymphoma - excessive production of lymphocytes by lymph nodes and spleen. eg: Hodgkins disease.

Malignant tumor - these tumors do not remain localized but invade other tissue and give rise to secondary tumors in other parts of the body (metastasis).

Why Cancer Is Potentially Dangerous

Brain

Melanoma cells travel through bloodstream Liver Melanoma (initial tumor)

If left untreated cancer can result in death..

Naming Cancers
Cancer Prefixes Point to Location
Prefix adenochondroerythrohepatolipolymphomelanomyelomyoosteoMeaning gland cartilage red blood cell liver fat lymphocyte pigment cell bone marrow muscle bone
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hemangio- blood vessels

Microscopic Appearance of Cancer Cells

Normal cell

Cancer cell
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Characteristic adaptive features of cancer cells : 1. Loss of contact inhibition Normal cells stop growing when their plasma membranes come into contact with one another - normal cells stop moving when they contact each other this is called contact inhibition, cancer cells lose the property of contact inhibition. Transformed cells do not stop dividing after forming a monolayer division continues until several layers of cells are formed.

2. Unrestrained control of growth Cancer cells lack the normal control systems to shut off unwanted growth.

3. Metastasis Metastasis is the spread of cancer cells from a primary site of origin to other tissues where they grow as secondary tumors.
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Some biochemical properties of cancer cells : 1. Increased glycolysis (Warburg effect)

Otto Warburg observed that virtually every type of cancer cells that form solid tumors excrete much larger quantities of lactic acid than its normal counterpart. This is known as the Warburg effect. Unlike normal cells, which break down sugar using oxidative pathways (or the Krebs cycle), tumor cells used nonoxidative pathways (glycolysis) to generate energy from sugar.

2. Alterations in cytoskeletal proteins Less organized/ disorganized arrangement of cytoskeletal proteins - such as myosin , tubulin etc.

3. Loss of anchorage dependence Cancer cells in culture can grow suspended in media while most normal cells need to attach to a substratum to grow (anchored).

4. Cancer cells are seemingly immortal Cancer cells in culture can continue to grow indefinitely.

The Somatic Mutation Theory Of Cancer Theodore Boveri 1914 He stated that the fundamental cause of cancer was in chromatin imbalance in the cells from which cancer arises. Evidence : Many cancers have chromosomal abnormalities

The cell cycle

What Causes Cancer?

What Causes Cancer?

Some viruses or bacteria

Some chemicals Heredity Diet Hormones

Radiation

Population-Based Studies
U.K.: Lung cancer

Regions of Highest Incidence

CHINA: Liver cancer

JAPAN: Stomach cancer U.S.: Colon cancer

CANADA: Leukemia

AUSTRALIA: Skin cancer

BRAZIL: Cervical cancer

A striking finding to emerge from population studies is that cancers arise with different frequencies in different areas of the world. For example, stomach cancer is especially frequent in Japan, colon cancer is prominent in the United States, and skin cancer is common in Australia. What is the reason for the high rates of specific kinds of cancer in certain countries?

Heredity? Behaviors? Other Factors?

(Number of new cases per 100,000 people)

Colon Cancer

Stomach Cancer
100 70
(Number of new cases per 100,000 people)

100

50

5 0

Japan Japanese families in U.S.

U.S.

7 0

Japan Japanese families in U.S.

U.S.

In theory, differences in heredity or environmental risk factors might be responsible for the different cancer rates observed in different countries. Studies on people who have moved from one country to another suggest that exposure to risk factors for cancer varies by geographic location. For example, in Japan, the rate of colon cancer is lower, and the rate of stomach cancer is higher, than in the United States. But this difference has been found to gradually disappear in Japanese families that have moved to the United States. This suggests that the risk of developing the two kinds of cancer is not determined primarily by heredity. The change in risk for cancer for Japanese families could involve cultural, behavioral, or environmental factors predominant in one location and not in the other.

Tobacco Use and Cancer

Some Cancer-Causing Chemicals in Tobacco Smoke

Low-Strength Radiation
High Dallas Skin Cancer Incidence Detroit Low Least

Pittsburgh

Annual Sunshine (UV radiation)

Most

Some atoms give off radiation, which is energy that travels through space. Prolonged or repeated exposure to certain types of radiation can cause cancer. Cancer caused by the suns ultraviolet radiation is most common in people who spend long hours in strong sunlight. Ultraviolet radiation from sunlight is a low-strength type of radiation. Effective ways to protect against ultraviolet radiation and to prevent skin cancer are to avoid going into strong, direct sunlight and to wear protective clothing. Sunscreen lotions reduce the risk of some forms of skin cancers.

High-Strength Radiation
High

Leukemia Incidence

Low Least X-ray Dose (atomic radiation)

Most

Increased rates of cancer also have been detected in people exposed to high-strength forms of radiation such as X-rays or radiation emitted from unstable atoms called radioisotopes. Because these two types of radiation are stronger than ultraviolet radiation, they can penetrate through clothing and skin into the body. Therefore, highstrength radiation can cause cancers of internal body tissues. Examples include cancer caused by nuclear fallout from atomic explosions and cancers caused by excessive exposure to radioactive chemicals.

Lag Time
20-Year Lag Time Between Smoking and Lung Cancer
Cigarette consumption (men)

4000 Cigarettes Smoked per Person per Year 3000 2000 1000

Lung cancer (men)

150 Lung Cancer 100 Deaths (per 100,000 people) 50

1900 1920 1940 1960 1980 Year

Chemicals and radiation that are capable of triggering the development of cancer are called carcinogens. Carcinogens act through a multistep process that initiates a series of genetic alterations (mutations) and stimulates cells to proliferate. A prolonged period of time is usually required for these multiple steps. There can be a delay of several decades between exposure to a carcinogen and the onset of cancer. For example, young people exposed to carcinogens from smoking cigarettes generally do not develop cancer for 20 to 30 years. This period between exposure and onset of disease is the lag time.

Viruses

Virus inserts and changes genes for cell growth Cancer-linked virus
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Examples of Human Cancer Viruses

Some Viruses Associated with Human Cancers

Bacteria and Stomach Cancer

Patients tissue sample

H. pylori

The bacterium Helicobacter pylori, which can cause stomach ulcers, has been associated with the development of cancer, so people infected with H. pylori are at increased risk for stomach cancer. Research is under way to define the genetic interactions between this infectious agent and its host tissues that may explain why cancer develops.

Heredity and Cancer

All Breast Cancer Patients

Inherited factor(s) Other factor(s)

Cancer is not considered an inherited illness because most cases of cancer, perhaps 80 to 90 percent, occur in people with no family history of the disease. However, a persons chances of developing cancer can be influenced by the inheritance of certain kinds of genetic alterations. These alterations tend to increase an individuals susceptibility to developing cancer in the future. For example, about 5 percent of breast cancers are thought to be due to inheritance of particular form(s) of a breast cancer susceptibility gene.

Heredity Can Affect Many Types of Cancer

Inherited Conditions That Increase Risk for Cancer

Inherited mutations can influence a persons risk of developing many types of cancer in addition to breast cancer. For example, certain inherited mutations have been described that increase a persons risk of developing colon, kidney, bone, skin or other specific forms of cancer. But these hereditary conditions are thought to be involved in only 10 percent or fewer of all cancer cases.

Cancer is a group of related diseases which are characterized by uncontrolled cellular growth and division

Cells divide when they should not divide and they lack the normal control systems to shut off unwanted cell division

How does cancer affect the human condition ?

CARCINOMA !!!

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"He who cures a disease may be the skill fullest, but he that prevents it is the safest physician
Thomas Fuller