Understanding Cancer

Most Cancers Are Not Inherited

Many people live in fear of cancer, often because one or more closely related family members have died from some type of cancer. They believe that cancer is passed on in the genes or that, at least, the susceptibility to cancer is inherited. Neither of these beliefs is correct for the vast majority of people. However, a constant fear of developing cancer can generate stress that may weaken the immune system and contribute to the development of disease, including cancer.

Scientific studies indicate that 90% to 95% of all cancers, including breast, lung, stomach, colon, skin, or prostate, are not inherited from parents except in a few rare families in which members do inherit one or more cancer-susceptibility genes.

Confusion often stems from misunderstanding the meanings of the words 'genetic' and 'inherited'. The two are not synonymous. All of your cells (except for red blood cells) contain exact copies of the chromosomes and genes that were in the fertilized egg from which you developed.

The genes in the chromosomes of any cell of your body, such as skin, lung, or stomach cells, can be chemically changed by environmental agents. These genetic changes in skin, lung, or stomach cells may transform them into cancer cells. Thus, cancer is a genetic disease in that genes are changed in a person's body cells; however, it is not an inherited disease because defective genes were not passed on from parents in most cases.

Even if several close family members have died of cancer, it does not mean that cancer 'runs in the family' and is an inherited disease. Currently, one out of every five deaths each year in the United States is due to cancer (American Cancer Society, 1997). If your parents and eight aunts or uncles died, probably two or three of them died of cancer simply by chance. If they all smoked cigarettes, it would not be surprising if more than three close relatives out of ten died of cancer.

One of the best pieces of evidence showing that most cancers are not inherited comes from a study of World War II veterans. The health of 15,000 pairs of identical or nonidentical (fraternal) twin brothers was followed for many years after WWII. No difference was observed in the different twin pairs in the development of cancer. That is, if one identical twin contracted cancer, his identical twin was no more likely to get cancer than the average person.

Because identical twins share identical genes (i.e., they are natural clones developed from the same fertilized egg), they should carry identical cancer-causing genes. The fact that identical twins do not both have cancer at significantly higher rates than fraternal twins (who differ genetically) both have cancer means that most cancers are not caused by inherited genes. For most people, life-style (e.g., diet, smoking, drinking alcohol) plays a far greater role in causing cancer than any genes that are passed on from parents.

Although only a fraction (estimates range between 5% to 10%) of all cancers are strongly influenced by heredity, some families do transmit cancer susceptibility genes to many family members. A cancer susceptibility gene does not cause cancer directly; however, it makes a person carrying such a gene more vulnerable to environmental factors that contribute to the risk of developing cancer.

Quite a few cancer susceptibility genes have been identified in recent years.

Most of these genes appear to contribute to the development of cancer in a particular organ: BRCA1 and BRCA2 genes are susceptibility genes for breast or ovarian cancer; APC, MSH2, and MLH1, for colon cancer. People who carry mutant (abnormal) copies of these genes are at higher risk for certain cancers than are people who carry normal copies (Toribara and Sleisenger, 1995).

Many genes that increase the risk of colon cancer have been identified and some of their biological functions in cells also are understood. If a person inherits an abnormal form of any one of three genes, APC, MSH2, or MLH1, the risk of colon cancer is increased. However, fewer than 5% of all colon cancer patients inherit any of these colon cancer susceptibility genes, so colon cancer is not inherited in over 95% of patients.

During a person's lifetime, mutations continue to arise and accumulate in cells lining the colon. For example, suppose a person inherited a MSH2 mutation and 20 years later a colon cell acquired an APC mutation. Those two mutations make that colon cell begin to reproduce itself at a faster rate; at some point, one cell among the faster growing ones acquires a third mutation in either a K-ras, DDC, or p53 gene. That cell now has three mutations and may become carcinoma of the colon. Along the way to tumor formation, other mutations also may occur. On average, when colon cancer cells are examined, they have at least three of the mutations. Now you can understand why chance genetic changes and exposure to environmental agents that cause them play such important roles in the development of cancer.

Environmental Factors

The causes of cancer or, more correctly, the risk factors associated with the development of cancer are numerous and complex (Shields and Harris, 1991). It often is difficult to point to a single cause of a cancer, but certain environmental factors are strongly correlated with the occurrence of particular cancers. Two examples are the strong correlation between cigarette smoking and lung cancer and exposure to ultraviolet (UV) light and skin cancer. Even in these examples, not everyone who smokes heavily or stays in the sun day after day will get cancer.

Epidemiology is the branch of science that investigates the causes and frequencies of diseases in human populations. Many epidemiological studies show that as many as 80% to 90% of cancers are caused by exposure to environmental factors that are known to increase the risk of cancer. For example, smoking cigarettes while young puts a person at 10 to 20 times higher risk of developing cancer later in life than persons who do not smoke. Eating fat-laden hamburgers and pizza frequently may be convenient, but it is ultimately unhealthy and may contribute to the development of certain cancers (Davis and Freeman, 1994). Because each of us can change our diets, stop smoking, and avoid other cancer-causing risks in the environment, preventing cancer is a realistic and attainable goal for most people.

Three classes of environmental agents—ionizing radiation, tumor viruses (viruses that cause cancer in animals), and chemical carcinogens (cancer-causing chemicals)—have been shown to increase the risk of cancer in both laboratory animals and people. Each of these agents increases the risk of cancer by producing chemical changes in genes, called mutations, that can occur in any cell in the body and cause it to grow abnormally. If a cell undergoes one or more mutations in genes that regulate its growth, it may begin to multiply rapidly and develop into a tumor. Environmental factors cause mutations and also affect the rate of abnormal cell growth.

Environmental factors change both genes and the growth properties of cells that may lead to the development of cancer.

Ionizing radiation consists of x-rays, UV light, and radioactivity whose energy can damage cells and chromosomes. The high rate of leukemia among survivors of the Hiroshima and Nagasaki atomic bomb blasts in 1945 leaves no doubt that radioactivity increases the risk of cancer.

In the United States, among children born in southern Utah in the 1950s who were exposed to radioactive fallout from nearby atomic tests, leukemia deaths were two to three times greater than among children born in southern Utah before and after the atomic tests. In a landmark legal decision in 1984, a federal court ruled that the U.S. government was negligent in conducting atomic bomb tests in southern Utah in the 1950s because they released radioactive material into the atmosphere. The court ruled that the families who were exposed to radioactivity as a result of these tests, and whose members died as a result of exposure to the radioactivity, were entitled to compensation.

The nuclear reactor accident at Chernobyl in the Ukraine in 1986 also released large amounts of radioactivity, particularly radioactive iodine, strontium, and cesium, into the atmosphere. Not only was the region around the reactor affected, but radioactive fallout occurred over much of Europe. In some countries, milk and crops were so contaminated that they had to be destroyed. Some of the radioactivity was detected in countries as distant as the United States and Japan (Shcherbak, 1996).

The toll in human sickness and deaths continues to mount even today. Approximately 32,000 persons died directly or indirectly as a result of the reactor explosion; another 30,000 suffered some degree of radiation sickness. Children are especially at risk from radioactive iodine, which causes thyroid cancer; in the Ukraine, thyroid cancer among children is currently 10 times higher than it was before the accident occurred.

The costs of this nuclear reactor accident cannot even be estimated; a final cleanup is still in progress and will cost hundreds of millions of dollars. This does not include any of the costs of human suffering, disease, or deaths. Nor does it include loss of enormous areas of land that are permanently unusable because of radioactive contamination. Even in the United States, the cost of disposal of radioactive wastes is never included in the cost of electricity generated by nuclear power when its costs are compared to other forms of generating electrical power.

Because any amount of ionizing radiation, however small, has the potential for causing damage to chromosomes and genes, one should minimize exposure to x-rays. For example, if you are healthy, periodic chest x-rays are unnecessary. Dental x-rays with each 6-month checkup also pose a cumulative risk. Some homes release radon, a radioactive gas present in some building materials. Long-term exposure to the invisible radon gas contributes to the risk of cancer.

The most common source of ionizing radiation is UV radiation in sunlight. Because children and young people tend to play in the sun, people acquire as much as 80% of their lifetime UV exposure by age 20.

Ultraviolet radiation in sunlight is characterized by two different wavelengths, called UVA and UVB. Until recently, it was thought that only UVB was dangerous, but now it appears that both forms of UV radiation are harmful. Reducing the time of exposure to intense sunlight and using sunscreen creams to protect exposed areas of the body reduce the risk of skin cancer.

In 1911 Peyton Rous, a scientist working at the Rockefeller Institute in New York, showed that cancer could be produced in chickens by injecting them with a virus isolated from tumors that occur in chickens. Since then, other viruses, called tumor viruses, have been found that cause cancer in animals such as mice, cats, and monkeys.

Finding tumor viruses that infect people has been generally unsuccessful despite a generation of research. Only four viruses have been associated with specific human cancers; in the vast majority of people, infection by these viruses will not cause cancer, although it will increase risk. Increased cancer risk is associated with infection by hepatitis B virus (liver cancer), papillomavirus (genital cancer), human T-cell leukemia-lymphoma virus (leukemia and lymphoma), and Epstein-Barr virus (cancer of the nose or pharynx).

A chemical carcinogen is an environmental chemical that can interact with cells to initiate cancer, usually by chemically altering the chromosomes or genes in cells. Genes are responsible for manufacturing the enzymes and other proteins a cell needs to function properly. An altered gene usually makes an abnormal protein that may change the growth properties of a cell and cause it to become a cancer cell.

Many chemicals that are developed are now tested to determine their cancer-causing potential. Unfortunately, many thousands of chemical substances already in use have not been adequately tested. Of the thousands of chemical substances that have been tested, many have been found to be carcinogenic and should be avoided if at all possible. Carcinogens include cigarette smoke, pesticides, asbestos, heavy metals (lead, mercury, cadmium), benzene, and nitrosamines.

Despite the long list of carcinogenic substances, some scientists and public health officials argue that tobacco is the only substance of consequence with respect to the numbers of cancers caused. While the argument has some basis, it is of small consolation to persons who acquire cancer from exposure, often without their knowledge, to carcinogenic substances in the environment or workplace.

In some industries, workers have cancers that almost never arise in the general population. For example, mesothelioma is a rare form of lung cancer that only occurs among persons exposed to asbestos fibers. Long-term exposure to the heavy metals beryllium and cadmium increases workers' risk of prostate cancer. Workers exposed to vinyl chloride, the starting material for polyvinyl chloride (PVC) pipes and other products, develop a rare form of liver cancer not found in the general public. Fortunately, with current occupational and safety regulations, these types of cancer occur infrequently.

The total number of cancers attributable to industrial chemicals is small compared to those caused by tobacco and diet, however, cancers caused by industrial chemicals are preventable or avoidable. Before you accept a job it might be wise to determine what chemicals you will be exposed to for long periods.

Estrogens are hormones that regulate a variety of biological functions in women, including the growth and development of breast tissue. Many chemicals that we are exposed to in the environment mimic the action of normal estrogen to some degree; such chemicals are called xenoestrogens (literally, foreign estrogen). Exposure to xenoestrogens in the environment may cause breast cancer (Davis and Bradlow, 1995).

Substances that contain xenoestrogens include the pesticides DDT (now banned in the U.S., but still used elsewhere), methoxyclor, kepone, chlordane, atrazine, and endosulfan. Polychlorinated biphenyls (PCBs), which were used in electrical transformers for many years, also are xenoestrogens. Bisphenol-A, a component of polycarbonate plastics that are widely used, can leach into liquids when the plastic bottles are heated. Even the gasoline vapor inhaled at the pump can act as a xenoestrogen.

A variety of evidence points to environmental xenoestrogens as possible agents in the formation of cancer. Clues came from wildlife that suffered reproductive abnormalities after being exposed to xenoestrogens. Male fish collected near the outflow from sewers showed production of vitellogin, a female protein. Alligators hatched in a lake in Florida contaminated with a pesticide grew abnormally small penises and had altered hormone levels. And military dogs that served in Vietnam (where Agent Orange, a xenoestrogen, was widely dispersed) have twice the rate of testicular cancer and reproductive defects compared with dogs that did not serve in Vietnam. So xenoestrogens may not only be involved in breast cancer, but may also play a role in reproductive problems and testicular cancer.

The effects of xenoestrogens can be tested on human cells grown in the laboratory. Normal estrogen binds to many cells and affects their growth. Xenoestrogens bind to the same cellular receptors as normal estrogen and exert some of the same effects on the growth of cells. The evidence that xenoestrogens can affect cell proliferation and reproductive organs is now well established.

Since 1976, when chlorinated pesticides were banned in Israel, and all pesticide residues eliminated from milk products, the incidence of breast cancer among Israeli women has been declining. Israel is the only industrialized country that has not experienced an increase in breast cancer in the past 20 years. These observations also lend support to the idea that xenoestrogens contribute to development of breast cancer.

However, a large study that included more than 100,000 nurses in the U.S. concluded that breast cancer is not associated with any differences in the level of PCBs (polychlorinated biphenyls) or DDE (dichloro-bischlorophenyl-ethylene), which are xenoestrogens. There was no significant difference in the levels of these chemicals in the blood of women with breast cancer compared with women who are healthy. Therefore, some medical experts now believe that the breast cancer risk resulting from xenoestrogens is very small (Safe, 1997).

It is impossible to avoid all exposure to xenoestrogens since they are everywhere in the environment. But certainly avoid any avoidable exposure. Also, eating broccoli, cabbage, and soy products may help counteract the effects of xenoestrogens. This advice comes from the observation that Asian women have much lower rates of breast cancer in comparison to white or black American women. Asian diets are richer in these vegetables, which may contain chemicals that block the biological activities of the xenoestrogens.

 

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