12.5: Cancer at Remote Sites

Once what we breathe, eat, and drink are absorbed, it’s hard to track their effects. They contact cells throughout the body and can be changed by the multitude of substances they encounter. It’s like trying to track quick-change artists entering the subway at rush hour.

Cancer of the bladder and liver are less common, but many of the cancer-causing agents in what we breathe, eat, and drink have been tracked there. Like cancer of direct-contact sites discussed earlier, bladder and liver cancer can reflect carcinogens in what we ingest and inhale.

Not much is known about causes of colon, breast, and prostate cancer, but these cancers have been linked to obesity and diets that are high in fat—especially animal fat. Keep in mind, however, that diets high in animal fats also tend to be high in protein and calories, and low in vegetables, fruit, and whole grains. Obesity is also more common in populations with high-fat diets. While obesity is linked to these cancers, a specific effect of obesity or a dietary component is hard to pinpoint.

Proof of a link isn’t proof that one factor causes the other. Animal studies have shown that tumors occur more often with high-fat diets, and that diets low in protein and calories suppress the development of tumors.

The advice is to aim for a healthy weight and eat a diet generous in plant foods and moderate in fat and protein (Chap. 4). Exploring the intricacies of how diet affects the risk of cancer is an active area of research.

For timely information on the causes, risk factors, treatment, etc., of various cancers, go to cancer.gov (National Cancer Institute), cdc.gov (Center for Disease Control and Prevention), and cancer.org (American Cancer Society).

Bladder Cancer

If a water-soluble substance can’t be used or broken down in the body, one of the only ways we can get rid of it is via the urine.* Any cancer-causing substance in the urine raises the risk of bladder cancer because urine is stored there. Bladder cancer is more common in men than in women. Evidence suggests that most bladder cancer in this country is caused by smoking and occupational exposures to carcinogens. Smoking is estimated to cause about one-half of all bladder cancers in both men and women.

People who work in jobs that expose them to certain chemicals used industrially (e.g., in processing paint, dye, metal, and petroleum products) have a higher risk of bladder cancer. The chemicals can be absorbed through skin and lungs. Drinking arsenic-contaminated well water and taking the Chinese herb Aristolochia fangchi can also cause bladder cancer.

^{*Analyzing urine is useful: Glucose suggests diabetes; it gets into urine when blood-glucose is abnormally high. Cotinine (a breakdown product of nicotine) is used to gauge a nonsmoker’s exposure to tobacco smoke. Protein indicates a kidney problem—kidneys aren’t doing their job of keeping protein out of urine.}

Liver Cancer

The liver is especially vulnerable to toxic substances. It’s hit with high levels of dietary substances because it’s the first organ the blood encounters after leaving the digestive tract (Figure 7.1). Also, many toxins are metabolized there (note that liver enzymes are an important part of the Ames test). It’s the main organ that breaks down alcohol, and is where many substances are altered, e.g., carcinogens are sometimes changed into innocuous substances and vice versa. Many fat-soluble substances (including fat-soluble carcinogens) concentrate in the liver, e.g., it stores more than 90% of the body’s vitamin A (a fat-soluble vitamin).† (Only water-soluble substances are excreted in urine.)

Excessive alcohol intake is a major risk factor for liver cancer, especially when combined with smoking or chewing tobacco. In developing countries, other liver toxins play a bigger role.

Aflatoxins are potent carcinogens thought to be a major cause of liver cancer in developing countries (they are fat-soluble and accumulate in the liver). They are made by common molds Aspergillus flavus and Aspergillus parasiticus and are natural contaminants of cottonseed, cereal grains, and peanuts, and are particularly found in improperly stored crops of peanuts and corn.

The Food and Drug Administration (FDA) has set the maximum permissible level of aflatoxin at 20 parts per billion (ppb) in our food. It is illegal to dilute a heavily contaminated batch of grain with a less contaminated batch to get below 20 ppb. As an extra measure of safety for infants and children, less aflatoxin is allowed in milk (0.5 ppb). Aflatoxin can get in the fat in milk, cheese, meat, etc., when contaminated grain is fed to the animals.*

Large amounts of aflatoxins have caused acute poisoning in countries like Thailand, India, Philippines, Uganda, Laos, China, and Taiwan. Places in the world where crops are heavily contaminated with aflatoxins are also places where liver cancer is common. In many areas, long-term risk of liver cancer often takes a back seat to the immediate problem of food scarcity.

A further complicating factor is that areas in the world where food is highly contaminated with aflatoxins are also areas where infection with hepatitis virus is common. Several viruses can cause hepatitis (inflammation of the liver). Those that cause hepatitis A, B, and C† are the most common (Table 12-3). Hepatitis can lead to liver cancer, so it’s hard to separate out the effect of aflatoxin alone. A worldwide vaccination program against hepatitis B in high-risk populations is helping prevent liver cancer, and is much more cost-effective than reducing aflatoxin contamination in developing countries. To learn more about hepatitis: cdc.gov/hepatitis/abc/

Table 12-3: Hepatitis A, B, C

^{† Many people take self-prescribed vitamin A supplements. Acute symptoms of toxicity include nausea, headache, blurred vision, and peeling skin. Arctic explorers have suffered from vitamin A toxicity from just a single meal that included seal or polar bear liver (exceptionally high in A).
*In 1989, many dairies had to dump milk (e.g., 400,000 lbs by Michigan farmers) contaminated as a result of the 1988 drought-induced aflatoxin infection of corn crops in the Midwest.}

Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women (Table 12-2). Genetic susceptibility plays a part in 10-25% of breast cancers; some of these genes have been identified. Also, women with dense breasts (more connective tissue than fat tissue) have a higher risk.

A major risk factor for all women is increasing age. A 70-year-old woman’s risk of breast cancer is about 10 times higher than that of a 30-year-old. Most breast cancers are diagnosed after age 50.

A woman’s reproductive history affects her risk through the timing and duration of various female hormones. Risk is higher with early age of first menstruation, late menopause, no children, and having a first child after age 30. All of these involve long stretches of uninterrupted, high estrogen levels. Menopausal hormone therapy of estrogen plus progestin also increases risk of breast cancer.

Another risk factor is being overweight/ obese. Overweight girls start menstruating earlier (a risk factor). At menopause, estrogen levels fall, and body fat then becomes a prominent source of estrogen. This increases the breast cancer risk for women who are overweight/obese after menopause.

It appears that a high-fat diet, per se, doesn’t increase the risk of breast cancer. However, large studies, such as a prospective study of more than 90,000 premenopausal women enrolled in the Nurses’ Health Study, suggest that a high animal fat intake in premenopausal women raises the risk of breast cancer.

Scientific evidence has been accumulating that alcohol increases the risk of breast cancer. A major analysis published in 2013 concluded that alcohol intake is responsible for about 15% of deaths from breast cancer in the U.S. One of alcohol’s effects on breast cancer could be via its effect on hormone levels (e.g., alcohol increases estrogen in premenopausal women).

A prospective study of 106,000 women enrolled in the Nurses’ Health Study (published in 2011) found that even low levels of alcohol intake were linked to higher risk of breast cancer, with the cumulative alcohol intake over a woman’s life being most closely correlated with increased risk. The study concluded that there was no “safe” level of alcohol intake, and the higher the total alcohol intake over the decades, whether when younger or older, the higher the risk of breast cancer.

There are trade-offs. Moderate amounts of alcohol (about 1 drink/day) is linked to a lower the risk of heart disease in older women, but older women are also at increased risk of breast cancer. Younger women are at higher risk of breast cancer than heart disease. We know a lot about how to prevent heart disease, but very little about how to prevent breast cancer. However, alcohol intake as a risk factor for breast cancer is something we can do something about.

^{*In 1989, many dairies had to dump milk (e.g., 400,000 lbs by Michigan farmers) contaminated as a result of the 1988 drought-induced aflatoxin infection of corn crops in the Midwest.}

Prostate Cancer

Less is known about prostate cancer than breast cancer. As in breast cancer, prostate cancer is linked to sex hormones (high testosterone), increasing age, and a high animal-fat diet.

Men with a diet high in animal fat have about a 2-fold higher risk of prostate cancer. Eating cooked tomato products is linked to a lower risk. This is possibly due to lycopene, a red carotenoid in tomatoes (carotenoids will be discussed shortly). It’s ironic that in the typical American diet, we eat most of our tomato products along with fat, e.g., pizza, catsup on fries, salsa with tortilla chips.

Black men have very high rates of prostate cancer (Figure 12.1, 12-2, 12-3)—about the highest in the world. Uncovering the reasons for this could tell us a lot about what causes prostate cancer and how to prevent it.

An intriguing theory is that inadequate vitamin D might be a factor. Blacks have more of the skin pigment melanin, which lessens sun-induced vitamin D production in the skin (Chap. 14). They also get less sun exposure than men in Africa, who have less prostate cancer. Also, many Black men avoid milk (vitamin D fortified) because of lactose intolerance.

Testicular Cancer

Cancer of the testicals isn’t very common, but is discussed here because it’s most common in young men, ages 20-44 (most cancers are more common at older ages). The cause is unknown. The only known risk factor is undescended testes at birth, which occurs in about 1% of males (ask your mom!) and typically is surgically corrected at about age one. Also, testicular cancer is much more common in White than in Black men.

When Lance Armstrong was diagnosed with advanced testicular cancer in 1996 at age 25, he was one of the top bicycle racers in the world. His recovery (with only about a 1% chance of recurrence) is a testament to both him and modern medicine. He was treated with surgery and intensive chemotherapy (after storing his sperm). He not only made a remarkable recovery from the cancer, but in 1999 he won the grueling 2,288-­mile Tour de France followed by 6 more wins (all of his wins were revoked due to doping). He also had 3 children with his wife by artificial insemination using his stored sperm.