Risk Factors – An Overview

At one time excessive consumption of coffee had been correlated with cancer of the pancreas, (l2) but considerable doubt has been cast upon this correlation. (l3,l4) Obesity is also an independent risk factor for cancer.

The mortality rate from lung cancer has been increasing since 1968, even though it has been known throughout that period that cigarette smoking is the major cause of the disease. It has been estimated that 30 percent of all cancers may be related to smoking, either directly or indirectly. The incidence of cancers of the lung, head and neck, esophagus, pancreas, kidney, and bladder is increased in people who smoke. The fifteen carcinogens that have been found in tobacco smoke include hydrocarbons and aromatic amines. People who work with asbestos or uranium or who drink alcohol have an increased risk and incidence of cancer if they also smoke. (This is called synergism, an action of two or more substances achieving a result of which each substance individually is incapable.) It seems reasonable then to explore ways to decrease the number of cancers related to smoking and other known human carcinogens by reducing the number of new smokers, encouraging current smokers to quit, and eliminating the other carcinogens altogether from our diet or eliminating our exposure to them.

Due to differences in their genetic make-up, individuals exposed to a carcinogen will not all have the same probability of getting cancer. Certain proteins from the liver, called enzymes, can break down or activate the carcinogen at different speeds in different people to either render it harmless or promote it to cause cancer. These enzymes will either destroy or activate carcinogens to varying degrees according to inherited tendencies. Some foods can induce certain enzymes to destroy certain carcinogens. The most potent food sources to induce these enzymes are vegetables of the Brassicaceae family, which includes Brussels sprouts, cabbage, and broccoli. (16)

Environmental Risk Factors

Environmental factors may be just as important as genetic factors for cancer. For example, Japanese men and women who leave Japan and settle in Hawaii or the continental United States have a lower risk of Stomach cancer than those who remain in Japan. Stomach cancer in the United States has been steadily decreasing with the advent of refrigeration and the consequent removal of carcinogenic chemicals as food preservatives.

Air pollution may be a risk factor for cancer, especially lung cancer. Those living in cities encounter many sources of pollution. More people in cities smoke cigarettes than in rural areas. Carcinogens derived from car emissions, industrial activity, burning of solid wastes and fuels remain in the air from four to forty days and thereby travel long distances. (17) And asbestos, a potent carcinogen, can also be found airborne in cities.

Our drinking water contains a number of carcinogens, including asbestos, arsenic, metals, and synthetic organic compounds. (18,19) Asbestos and nitrates are associated with gastrointestinal cancers; arsenic is associated with skin cancer; and synthetic organic chemicals are associated with cancers of the gastrointestinal tract and urinary bladder.

As with many carcinogens, the time between exposure to the carcinogen and actual development of cancer may be quite long. Hence, the cause of a cancer initiated by trace amounts of either airborne or waterborne carcinogens years before the cancer appears may be attributed to an unrelated or unknown cause at the time of diagnosis. We are able to detect many carcinogens in our environment, but many others exist in low concentrations. These environmental carcinogens may themselves cause cancer in certain individuals, or they may interact with other risk factors to initiate, or promote, cancers. Therefore, our imperfect environment, a risk factor for cancer, must be modified. If we avoid introducing harmful substances into the environment, it will remain clean.

Radiation Risk Factors

Human studies show that the more radiation a person is exposed to, the higher is the risk of developing cancer, especially if the radiation exposure is to bone marrow, where the blood cells are made. People who received radiation to shrink enlarged tonsils or to treat acne have a higher risk of developing cancer of the thyroid and parathyroid glands located in the neck. Survivors of the bombings of Hiroshima and Nagasaki have had an increased incidence of leukemia, Iymphoma, Hodgkin’s disease, multiple myeloma, and other cancers. People who used to paint radium on wristwatch dials have a high incidence of osteogenic sarcoma, a bone cancer. Chronic exposure of fair-skinned, easily sunburned people to sunlight (ultraviolet light) will lead to a higher rate of skin cancer.

There has been mounting concern that people who work in or live near nuclear power plants have a higher risk of developing cancer. In the United Kingdom a higher incidence of childhood leukemia has been reported in children living near several nuclear facilities, most notably a fuel reprocessing plant located at Sellafield in northwest England. (20) The results of another study involving over 8,000 men who worked in the Oak Ridge National Laboratory in Tennessee between 1943 and 1972 show that these men had a higher risk of developing cancers, especially leukemia. (21) Another study shows no such increase in cancer incidence. (22)

Women with tuberculosis who received many chest X rays to follow the progress of treatment had an increased incidence of breast cancer with as little as 17 cGy total dose. A cGy, or centiGray, is a defined amount of energy absorbed by a certain amount of body tissue. One chest X ray using modern equipment delivers about 0.14 cGy. Riding in an airplane at 35,000 feet for six hours exposes a person to 0.01 cGy.

A study by Matanoski published in the Proceedings of the 1980 International Conference on Cancer indicates that radiologists, besides their well-known increased risk of developing cancer, may also have a 30 percent increased risk of death from cardiovascular disease and stroke due to radiation exposure. Workers in many industries are chronically exposed to low-dose radiation and hence may be at risk for heart disease and cancer. We may therefore have to reexamine standards for acceptable radiation levels in industry.

Occupational Risk Factors

About 10 percent of all cancers are related to exposure to carcinogens on the job The relationship between a person’s job and cancer was noted in the eighteenth century when it was observed that the incidence of cancer of the scrotum was very high in chimney sweeps. Many associations between exposure to carcinogens at work and cancer have been made since then. Most recently the boot and shoe manufacture and repair industry and the furniture and cabinet-making industry were shown to be risk factors for cancer of the nasal sinuses. (23)

Preliminary studies indicate that butchers and slaughterhouse workers are at risk for lung cancer and cancer of other parts of the respiratory system as well as some leukemias. (24,25) However, these findings need to be confirmed and controlled for those persons who also smoke before this industry can be labeled as a definite risk factor for cancer. Other occupations and their associated human cancers are listed in Table 2.1.

Age as a Risk Factor

The older you get, the higher is your risk of developing cancer. Your risk for cardiovascular disease also increases with age, but to a greater degree. The Biometry Section of the National Cancer Institute has presented studies which show that with every five-year increase of age there is a doubling in the incidence of cancer. (26) The elderly often Suffer from nutritional deficiencies, and they have an increased num-ber of infections, autoimmune diseases, and infantile disease patterns, as well as cancer. Werner’s syndrome, which prematurely ages very young children so that they die in early adolescence, is characterized by an impaired immune system. These facts suggest that the immune system (see Chapter 4) in the elderly is working inefficiently, partly due to poor nutrition. (27) Because the gastrointestinal tract absorbs nutrients less efficiently with age, the elderly need more nutrients in their diets.

As you get older, your risk of getting cancer increases not only because of your age but also due to the amount of time you have been exposed to external risk factors. For example, cigarette smoking increases your chances of getting lung cancer. The longer you smoke, the greater is the likelihood and incidence of lung cancer. For men between 55 and 64, the annual lung cancer mortality rate is five times higher if they started to smoke before age 15 than if they started to smoke after age (25-28) If a person stops smoking, there is a decreased risk of developing lung cancer, but this risk does not go back to zero.

Table 2.3 lists the number of people aged 65 or more for approximately each decade beginning with 1980. By 2030 the number of Americans in this age bracket will more than double the number in this group today.

Atherosclerosis and Cancer

Atherosclerosis and its many complications are the most common cause of death in the United States. Atherosclerosis, commonly called ”hardening of the arteries,” is a disease that narrows the inside diameter of the artery. This narrowing restricts the blood flow beyond the narrowed portion, therefore less oxygen can be delivered to those tissues by the red blood cells. Death of tissues occurs when they receive little or no oxygen. The less oxygen, the more dead tissue. Pain is a symptom of either very low oxygen supply to tissues or outright death of tissues. This is why a person having a “heart attack” is in a lot of pain: some tissues are dying and others are not receiving enough oxygen. What does atherosclerosis have to do with cancer? Well, cancer may be responsible for the development of heart and vessel disease in a way, and conversely high blood pressure (a form of blood vessel disease) may lead to the development of cancer under certain circumstances.

The first step in the formation of a narrowed artery is the manufacture of cells (smooth muscle cells) which line the inside of the artery. Then cholesterol gets deposited in these cells after they have increased in number. The increased cells together with cholesterol is called a plaque. There is good evidence that these cells come from a single cell, that is, they are cloned from one common cell. Cloning is a form of cancer. (30) This situation can be produced in chickens by feeding. them carcinogens (benzo(a)pyrene and dimethylbenzanthracene), chemical substances that produce cancer. These particular carcinogens cause an increase in the number and rate of formation of plaques without altering the blood level of cholesterol. In humans, these types of carcinogens (hydrocarbons) are carried by certain proteins (low density lipoproteins) which also carry cholesterol. More curiously, an enzyme called aryl hydrocarbon hydroxylase, present in cells of the inner walls of arteries, can activate hydrocarbon carcinogens to start proliferating the lining cells. (31) Therefore, if we eat food contaminated with these hydrocarbons or are otherwise exposed to them so that they get into our bloodstream, atherosclerosis may begin to develop. Of course this is just one of many factors involved in the development of atherosclerosis.

R.W. Pero and colleagues have shown a relationship between high blood pressure and cancer. (32) The study shows that the higher the blood pressure and the older the person, the more alterations of DNA that occur in cells. The more abnormal the DNA content of a cell, the snore often it will lose control and develop into a cancer. There is some evidence that people with high blood pressure have an increased risk of developing breast cancer, (33) colon cancer, lung cancer, and other cancers.

Hormonal Risk Factors

Hormones influence a cell’s growth and development, so if there is an excess or deficit of hormones in the body, then cells will not function properly and may grow abnormally or aberrantly and become cancer cells.

Women who have never been pregnant have a higher risk of developing breast cancer than women who do have children; and women who become pregnant before age 20 have a reduced risk. Women whose mothers or other close relatives have breast cancer have three times the normal risk of getting breast cancer. Women who do not menstruate during their lifetime have a three to four times higher risk of developing breast cancer after the age of 55. A lower risk of breast cancer is seen in women whose ovaries cease to function or are removed surgically before age (35).

There has been considerable controversy over whether oral contraceptives can cause breast and liver cancer. Many studies seem to indicate that hormones used in birth control pills are a risk factor for breast or liver cancer. (35,36) Estrogens in these oral contraceptives can cause benign liver growths as well, which can bleed extensively and cause problems related to bleeding.

Daughters of women who received DES (diethylstilbestrol) therapy during pregnancy have developed cancer of the cervix and vagina. Sons of women who took DES have a higher risk of developing cancer of the testicles because DES causes urinary tract abnormalities including undescended testicles, which, if not corrected surgically before age 6, can develop into cancer of the testicles. (37) Furthermore, women exposed to these same synthetic estrogens in adult life have a higher risk of developing cancer of the cells that line the inside of the uterus (endometrial cancer). Male hormones can predispose to both benign and malignant liver tumors.

Obesity is directly correlated with breast cancer (38-41) and endometrial cancer. (42)

Fibrocystic breast disease, a benign disease that affects 50 percent of all women sometime during their lives, probably represents a hormone imbalance. If a woman has had the disease over many years, she is at an increased risk of developing breast cancer. (43,44) Recently, fibrocystic breast disease has appeared to respond to certain nutrients and dietary modification.

Sexual-Social Risk Factors

Cancer of the cervix is associated with having sexual intercourse at an early age and with having multiple male sex partners. The earlier the age of the female when she first has sexual intercourse, and the greater the number of male partners she has, the higher is her risk of getting cancer of the cervix. Sexual intercourse with uncircumcised male partners may also contribute to a woman’s risk of developing cervical cancer.

Cancer of the penis is a very rare disease in the United States. There is almost universal agreement that one primary risk factor is responsible for this cancer–poor hygiene, especially in the uncircumcised male. Secretion and different organisms retained under the foreskin produce irritation and infection, which are thought to predispose to cancer cellular changes. (45)

There is an epidemic outbreak of Kaposi’s sarcoma in sexually active male homosexuals. (44-48) Kaposi’s sarcoma is a cancer of the skin, mucous membranes, and Iymph nodes. Those affected have an acquired immunodeficiency syndrome (AIDS). In addition to Kaposi’s sarcoma, male homosexuality is a risk factor for two other cancers: cancer of the anus (49) and cancer of the tongue.

Sexually active male homosexuals in good health can have a normal or abnormal immune system. Many with an abnormal immune system appear quite healthy. Some with a malfunctioning immune system have had Kaposi’s sarcoma and/or fatal or life-threatening infections caused by Pneumocystis carinii. (50,51)

The immune impairment from AIDS seen in sexually active male homosexuals, intravenous drug users, prostitutes, and heterosexuals is now clearly related to infection by the HIV virus. Other risk factors leading to human susceptibility to HIV include amyl nitrite, a drug used as a sexual stimulant. Amyl nitrite produces a profound impairment of the immune system, especially the T Iymphocytes. (52) Also, immunological abnormalities are seen more often in homosexuals who have many sexual partners than in those who have only one partner.

Viral Risk Factors

Viruses have been shown to directly cause cancer in fish, birds, frog* and almost every mammal. Over one hundred viruses capable of causing cancer have been identified. Two human cancers, T cell leukemia and T cell Iymphoma, have been shown to be caused directly by viruses. Perhaps all the other white blood cell tumors will also be shown to be caused by viruses.

In the following chapters we will review nutritional risk factors, other risk factors that can lead to the development of cancer, and ways that the risk factors can be modified.

A person in a high-risk category will not necessarily develop cancer. The high-risk category indicates only that a person in it is more at risk than a person in another category.

Following are a few examples of persons with various risk factors, their relative degrees of risk for developing cancer, and what they should do to modify those risks and thereby reduce their chance of developing cancer (and/or cardiovascular disease). After each risk factor the score is indicated in parentheses.

Consider Linda, a 56-year-old (C) New Jersey (B) housewife (O). She is 5 feet 5 inches tall, weighs 160 pounds (B), eats red meat daily, eats several eggs per week, drinks milk daily, consumes very little fiber-containing foods, and does not eat a balanced diet (A). She also smokes two packs of cigarettes a day, which has done for over fifteen years (A). Linda drinks socially (0) and has never had cancer (0), but her mother had breast cancer (B). She started having sexual intercourse at age 20 (0), first got pregnant at age 24 (0), has a history of fibrocystic breast disease (C), never had any radiation (0), and is relatively easygoing (0).

SELF-TEST

What is your risk of developing cancer? Take the following Cancer Risk Factor Assessment Test to determine your risk according to your diet, weight, age, lifestyle, and other factors discussed in this chapter. After you assess which factors pose a risk, you can begin to modify them according to my recommendations. Then take the test again to see if your overall risk has been reduced.

Linda’s total score is 2 A’s, 3 B’s, and 2 C’s. She is in the high-risk group. What can she do to modify her risk factors? She directly controls the most serious ones. I would advise her to terminate cigarette smoking abruptly and completely. Then I would suggest that she permanently modify her diet in order to reduce two other serious risk factors: her high-animal-fat, high-cholesterol, low-fiber diet, and her overweight problem. This would serve also to counter any weight gain that may occur when she stops smoking. Linda has no control over her age, the state in which she has lived, or her history of fibrocystic breast disease; but these are minor risk factors. By modifying the risk factors that she directly controls, over the course of time she will lessen her overall risk category and reduce her risk of developing cancer or cardiovascular disease.

The second example is Dave, a 24-year-old sexually active male homosexual who has many male partners and uses a drug called amyl nitrite (C). He smoked two packs of cigarettes a day for eleven years but quit one year ago (A). Up until a few months ago, he ate red meat daily, ate cheese daily, ate very few fiber-containing foods, and took no vitamins (A). His weight is normal (0), and he has never had cancer (0) nor have any of his family members (0). Until Dave was 21 years old he lived in Alaska (0), but he has since lived in New York City.

Dave’s total score is 2 A’s, zero B’s and 1 C. He is in the high-risk group, but by continuing not to smoke and by modifying his diet, he can dramatically lessen his overall risk.

Next is Nancy, a 27-year-old woman who smoked two packs of cigarettes a day until she quit eight years ago (B). She eats a well balanced diet consisting of red meat five times a week, low-fat dairy products, and an average intake of fiber (B), and she is 20 pounds overweight (C). As a lifelong resident of Vermont (C), Nancy has been working in the furniture industry for the past seven years (B). She is taking birth control pills (B) and has been doing so for the past ten years. She is fair-skinned, sunburns easily, and enjoys sunbathing and using a suntanning booth year-round (B).

On the surface of things it looks as though Nancy’s overall risk is not so bad, but when you examine the whole picture, you find she is in the moderate-risk category. Her total score is 5 B’s and 2 C’s. However, she is on the right track. She should do the following to modify her risk factors and thereby reduce her overall risk: continue not to smoke, lose 20 pounds, modify her nutritional status, seek another means of birth control, use sun screens to sunbathe, and avoid suntanning booths.

The last example is Bob, a 50-year-old (0) male chemist (B) who is 25 pounds overweight (B) and a meat-and-potatoes man all the way (A). He has smoked two packs of cigarettes a day for the past thirty years (A), drinks 4 ounces of whiskey every day (A), has lived in Illinois most of his life (B), and is easily angered (C). His father died of lung cancer (B).

You know that Bob is in the high-risk category: 3 A’s, 4 B’s, and 1 C. As you can see, he does have risk factors that he can directly control. He should do the following: stop smoking, drastically modify his diet and lose weight, consume alcohol in- moderation, and learn how to relax. All these modifications will greatly reduce his overall risk.