Prostate Cancer

Description

Alternative Names

Risk Factors

The major risk factors for prostate cancer include genetic, dietary, and environmental factors that effect male hormones (androgens) and make a man more susceptible to this cancer.

Age

Prostate cancer is the most common cancer in the US after skin cancers. It is also the second leading cause of cancer deaths among men. More than 220,000 new cases are reported each year, and, as the population ages, this number is expected to significantly increase. Prostate cancer occurs almost exclusively in men over the age of 40 and most often after the age of 50. It is estimated that by age 70, about 65% of men have at least microscopic evidence of prostate cancers. Fortunately, the cancer is often very slow growing and older men with the cancer nearly always die of something else.

Family History and Genetic Factors

Some evidence has suggested that heredity may play a role in prostate cancers. Men with a family history of the disease have a higher risk of developing prostate cancer. Having one family member with prostate cancer doubles a man's own risk and having three family members poses an 11-fold risk for the disease.

A number of genes are under investigation but the genetic mechanism appears to be very complex. Some early-onset cases of prostate cancer associated with specific inherited genes have been identified, but they account for a small percentage of cases.

A gene is a short segment of DNA which is interpreted by the body as a plan or template for building a specific protein. Genes reside within long strands of DNA which in turn make up the chromosomes.

Ethnicity

African American men have the worlds highest risk for prostate cancer, more than 50% higher than the risk for Caucasian American males. The disease is also more lethal among African Americans. Of note, men who live in Asia have lower risks for prostate cancer, but their risk increases if they move to North America. Thus, there are unknown environmental or dietary factors that can alter a man's underlying genetic risk of developing this disease.

Socioeconomic Issues. The higher mortality rates in African American men may be partly due to socioeconomic factors, such as lack of insurance, irregular screening and a late diagnosis, and unequal access to health care. For example, a 2000 study at a Veterans hospital where all the men had equal care reported no differences in tumor properties between African American and Caucasian men.

Dietary Factors.. Dietary factors may play some small role in the higher risk in African men. This is suggested by the fact that prostate cancer is rare in many parts of Africa.

Biologic Factors. Some evidence suggests that African American and Asian men have certain genetic factors that may affect male hormones differently and so help account for the higher risk in the first group and the lower risk in the second. Other research reports that African American men have lower levels than Caucasian men of a protein called insulin-like growth factor binding protein 3 (IGFBP3), which may protect against cancer. (Insulin-like growth factor-I is a hormone that may increase the risk for prostate cancer in any man.) Still, evidence is weak on such genetic and biologic differences and more research is needed.

Higher PSA Levels. African American men also tend to have higher PSA levels than Caucasians. They are overdiagnosed with prostate cancer by 37% compared to 15% in Caucasians using PSA screening tests.

High Exposure to Chemicals and Electromagnetic Fields

Chemicals. The relationship between prostate cancer and chemical exposure is controversial. Men whose work involves heavy labor and those exposed to certain metals and chemicals, including cadmium, dimethylformamide, and acrylonitrile, may be at higher risk for prostate cancer. Some studies have indicated that farmers might be at higher risk.

A 2001 study of data collected between 1979 and 1985 concluded that certain leisure activities may expose men to the same chemicals as those that pose a possible danger in the industrial setting. They included the following:

• Home or furniture maintenance.
• Painting, stripping, or varnishing furniture.
• Activities that involve exposure to lubricating oils or greases, metal dust, or pesticides or garden sprays.

Infection and Inflammation

Specific genetic factors that affect the body's response to viruses have also been associated with inherited prostate cancer cases. Some association has been seen between prostate cancer and bacterial or viral infections, such as herpesvirus, human papillomavirus, and cytomegalovirus. Although some of these agents are sexually transmitted, the association with sexual activity is still unclear. One theory suggests that in men with such genetic susceptibilities, any sexually transmitted infection can produce a chronic inflammatory condition in the prostate, which, over time, can initiate cancerous changes. Such beliefs are supported by a possible lower risk in men who take nonsteroidal anti-inflammatory drugs (NSAIDs). More research is needed.

Other Factors Associated with Prostate Cancer

Nonmelanoma Skin Cancers and Sunlight. One study reported that patients with prostate cancer and a history of nonmelanoma skin may have a higher risk for a poorer outlook. Such skin cancers are highly associated with exposure to sunlight. It should be noted, however, that sunlight triggers production of vitamin D in the body, which may help protect against prostate cancer. Prostate cancer rates are, in fact, lower in southern, sunny regions.

Vasectomy. Because testosterone levels remain higher for a longer period in men who had vasectomy, experts have postulated that such men have a greater chance for developing the cancer. A 2002 meta-analysis of 22 studies indicated a higher risk with vasectomy, but most recent studies are reporting no higher danger.A rigorous 2002 study from New Zealand, for example, which has the highest vasectomy rates in the world, found no increased risk of prostate cancer from the procedure, even 25 years after the operation.A 2002 study in California, in fact, reported a lower risk for prostate cancer in men who had had vasectomies. It is possible that the higher rates reported in the early studies may simply be due to earlier prostate screening in men who have had vasectomies. Indeed one study reported that about 25% of physicians screened men with vasectomies earlier for prostate cancer than those without the operation. [For more information,see Well-Connected Report #37 Vasectomy.]

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Dietary Factors

A Western lifestyle is associated with prostate cancer, so obesity, high-meat intake, and dietary fats have been intensively studied. Results have been inconsistent, however. Certain factors, such as carcinogenic compounds in well-cooked meat or high-calorie intake, may help explain the associations between such dietary factors and cancer risk.

Obesity and High-Calorie Intake. A 2001 study reported that obesity was associated with a modest increase in prostate cancer mortality, although not with the risk for prostate cancer itself. Some evidence suggests that it is a high-calorie intake rather than obesity or fat intake increases the risk for prostate cancer.

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Fats. Some, but not all, studies have found some association between high fat-intake and prostate cancer. This association may be explained by other suspected dietary factors for prostate cancer, such high-calorie diet, high meat intake, and calcium (found in dairy products), which are all also associated with fat intake. The effects of specific fatty acids (compounds that make up fats) may also help clarify the role of fats in prostate cancer.

• Omega-3 Fatty Acids. Some research has suggested that omega-3 fatty acid may be protective. Omega-3 fatty acids are found in plants (e.g., soybeans, rapeseeds [canola oil], flaxseed, and certain nuts and seeds) and fish oil (e.g., salmon, sardines, halibut, swordfish, and tuna). Some studies have reported a lower risk for prostate cancer in men who ate fish frequently (two or more times a week).
• Alpha-Linolenic and Omega-6 Fatty Acids. On the other hand, some research has indicated that alpha-linolenic acid and total omega-6 fatty acids may increase the risk of prostate cancer. Sources of these fatty acids are the polyunsaturated vegetable oils (e.g., corn, safflower, soybean, canola, and sunflower oil), which constitute most of the oils consumed in the U.S.

Meat and High-Temperature Cooking. Some evidence suggests that a high intake of red meat raises the risk for prostate cancer (also possibly colon cancer). Because red meat is often in fat, such findings may explain the inconsistencies found in studies that simply look at fat content as a risk for prostate cancer. Perhaps of more importance, high-temperature cooking (grilling, broiling, or pan-frying) of meat or poultry has been specifically associated with increased risk for cancer in some studies, Over-cooking meat increases the amount of compounds called heterocyclic amines, which has been associated with cancerous changes in general and prostate cancer in particular, at least in some studies. Cooking meats in liquid does not appear to increase these compounds. As with all dietary studies, some have observed no association between high intake of well-cooked meat and prostate cancer. Thus, this is a controversial area that requires more research

Vegetarian Diet. Small studies suggest that a vegetarian diet may be protective. Specific foods may be especially helpful in reducing the risk prostate cancer:

• Whole grain cereals, seeds, and nuts have been associated with a lower risk for prostate cancer. Part of this protection may be due to their high fiber content. Fiber binds to sex steroids and is excreted, carrying the hormones with it. Whole grains also contain selenium, a rare element that may have some protective properties.
• Many studies have reported a significantly lower risk for prostate cancer with high intake of cooked tomatoes, which are high in a beneficial plant chemical called lycopene. (Some studies have not reported such protection, although intake may have been too low.)
• Soy may also be protective, which may partially explain the low rate of prostate cancer observed in Japanese men and vegetarians (who typically use soy as a protein replacement). Theoretically soy, which is a rich source of an estrogen-like plant compound, may inhibit hormones that promote prostate cancer. Laboratory studies are mixed on such effects, however. Bowman-Birk inhibitor is a soybean-derived product that is being investigated for its effects on prostate health and possible prevention of prostate cancer. A 2001 trial of a concentrated form was associated with a decrease in serum PSA levels and in prostate volume. There is some concern, however, that such agents may increase the risk for pancreatic cancer.
• Cruciferous vegetables (e.g., cauliflower and broccoli) have cancer-fighting chemicals.
• Boron-rich foods (e.g., nuts, red grapes, avocados, and dried fruits) may also be protective.

Dairy Products, Calcium, and Vitamin D. Studies have reported an association between consuming large amounts of dairy products and a modestly increased risk for prostate cancer. (Moderate intake has not been associated with a higher risk.) That is some evidence that calcium (contained in dairy products) may increase the risk for prostate cancer by reducing levels of the most active form of vitamin D (1,25 dihydroxyvitamin D), which may protect against prostate cancer. In fact, some research is focusing on prostate treatments using vitamin D analogs. There is still no clear proof, however, that high calcium and low vitamin D levels pose a significant risk for prostate cancer. And, it should be noted that evidence strongly suggests that calcium reduces the risk for colon cancer.

Getting enough calcium to keep bones from thinning throughout a person's life may be made more difficult if that person has lactose intolerance or another reason, such as a tendency toward kidney stones, for avoiding calcium-rich food sources. Calcium deficiency also effects the heart and circulatory system, as well as the secretion of essential hormones. There are many ways to supplement calcium, including a growing number of fortified foods.

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Vitamins and Mineral Supplements

Vitamin E. Vitamin E is being investigated for possible protection against prostate cancer. To date, four trials have found that vitamin E may provide some reduction in risk for past and current smokers and for men with vitamin E deficiencies. Of concern was an association in one study of a higher risk for aggressive prostate cancer in nonsmoking men who took high doses of vitamin E (100 IU or greater).

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Selenium. Selenium is a trace mineral found in Brazil nuts, most red meats, poultry, shellfish, and dark mushrooms. In laboratory studies, selenium has acted directly on prostate cancer cells, stimulating cell death and inhibiting growth. In one 2003 study, selenium levels were measured in toenail clippings. Those with the highest levels had the lowest risk for prostate cancer. The findings were particularly pronounced in ex-smokers. Other studies on significant protection from selenium supplements against prostate cancer, however, have been weak. It is possible that supplements may benefit only those who have selenium deficiencies.In any case, as with other dietary factors, selenium alone is unlikely to be significant in protection against prostate cancer. It should be noted that high amounts of selenium can be toxic, and can cause hair and nail loss. It has also been associated with a higher risk for skin cancer.

Zinc. Zinc is of interest because it accumulates to the highest levels in a mans body in either a normal prostate or one enlarged from benign prostate hyperplasia. Some laboratory studies suggest that zinc might inhibit activation of prostate cancer cells. A 2003 study, however, reported that men taking zinc supplements in high doses (100 mg) had a higher risk for advanced prostate cancer. Of note, such men also took higher levels of calcium, iron, and other supplements that might have biased these results. More research is needed to determine the role of zinc on prostate health.

Alcohol

Moderate to heavy alcohol intake (22 to 56 drinks a week) has been associated with increased risk.

Exercise

Exercise is beneficial for general health and it temporarily lowers testosterone levels. Studies on its effects on prostate cancer are mixed. It may not have much effect on men who are at low risk to begin with. A 1998 study suggested that although exercise had no protective effect overall on prostate cancer, vigorous exercise was associated with a lower risk for metastatic prostate cancer. Exercise is an important component of any health-protective program.

Finasteride (Proscar)

Finasteride (Proscar) blocks an enzyme that converts testosterone to dehydroepiandrosterone (DHEA), the form of the male hormone that stimulates the prostate. The agent is used to shrink the prostate in men with benign prostatic hyperplasia. It is, therefore, being investigated for prevention of prostate cancer. A large 2003 study suggested that taking it may reduce the risk for prostate cancer by 25%. (On the negative side, the drug can impair sexual function.) The study had some problems, however. For example, in the placebo group, the rate of prostate cancer was much higher than in other studies. Comparing the lower risk from Proscar to other studies, then, would make the reduction less significant. Also when men taking Proscar did develop prostate cancer, the tumor cells tended to be aggressive types. Experts are investigating whether this observation has any significance. One possibility is that the drug actually stimulates high-grade cancer cells. Until more is known, experts do not recommend this agent for prevention.

Sexual Activity

Frequent ejaculations from masturbation or sexual activity has been associated with a lower risk for prostate cancer. Some experts speculate that certain carcinogens may be concentrated in prostate fluid, so that frequent ejaculation helps eliminate them. Of note, risky sexual activity, such as with multiple partners, increases the risk for sexually transmitted disease, which in turn may increase the risk for prostate cancer.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

There is some evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) offer some protection against prostate cancer. NSAIDs suppress chemical in the body called COX-2, a protein that may cause prostate cancer cells to spread. Standard NSAIDs include aspirin, ibuprofen (Advil), and naproxen (Aleve, Naprosyn, Naprelan, Anaprox). Many other NSAIDs, such as sulindac (Clinoril), are available only by prescription and are being studied for protection. Newer agents, such as celecoxib (Celebrex), rofecoxib (Vioxx), valdecoxib (Bextra), and meloxicam (Mobic) may warrant specific investigation. A 2002 study reported a 50% reduction in the risk for prostate cancer in men over 60 who took a daily NSAID, although conclusive evidence is still needed.