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 occurs almost exclusively in men over age 40 and most often after age 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

Evidence suggests that heredity plays a role in some types of prost ate 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.

In 1998, scientists discovered a gene, located on chromosome 1, which may be involved in 1 in 500 cases of prostate cancer. They named this gene HPC1. (HPC stands for “hereditary prostate cancer”.) In 2005, scientists announced another major breakthrough in understanding the genetic components of prostate cancer. Research published in Science suggested that, in some cases, prostate cancer occurs when a specific set of genes merge. The genes are part of the ETS gene family. At this point, scientists have identified 3 genes: ETV1, ETV4, and ERG. Doctors hope that future genetic research will help develop targeted drug therapy for prostate cancer.

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 world's 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. Men who live in Asia have lower risks for prostate cancer, but their risk increases if they move to North America. This indicates that 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 veteran's hospital where all 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:

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

Infection and Inflammation

Scientists think that specific genes that affect the body's response to viruses may be associated with certain types of prostate cancer. Some theories suggest that there may be a relationship between prostate cancer and infections such as herpesvirus, human papillomavirus, and cytomegalovirus. In 2006, scientists identified a new virus, XMRV, which is 30 times more common in men with prostate cancer who have a genetic mutation with the HPC1 gene. Scientists know that men who have the HPC1 genetic mutation are more likely to get prostate cancer. This new research suggests that the genetic mutation may make them more vulnerable to a virus that causes the cancer. Researchers will continue to investigate XMRV and other possible infectious causes of prostate cancer.

Other Factors Associated with Prostate Cancer

Obesity. Obesity may increase the risk for prostate cancer, particularly more aggressive forms of the disease. Obesity may also make prostate cancer more difficult to diagnose. A 2005 study found that overweight and obese men were more likely to be diagnosed with advanced prostate cancer and to die of the disease than normal-weight men.

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 review 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 doctors screened men with vasectomies earlier for prostate cancer than those without the operation. [For more information, see In-Depth 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 cancer-causing compounds in well-cooked meat or high-calorie intake, may help explain the associations between such dietary factors and cancer risk.

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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. The omega-3 fatty acids in fish (EPA and DHA) and the omega-3 fatty acids found in certain vegetables (ALA) can all protect the heart, but they may have different effects on the prostate.

• Marine Omega-3 Fatty Acids. Research indicates that docosahexanoic acid (DHA) and eicosapentaneoic acid (EPA), the omega-3 fatty acids found in fish, may be protective against prostate cancer. Some studies have reported a lower risk for prostate cancer in men who ate fish frequently (two or more times a week).
• Alpha-Linolenic Acid. On the other hand, some research has indicated that alpha-linolenic acid (ALA), the omega-3 fatty acid found in certain plants and nuts (flaxseed, canola, walnuts), may increase the risk of prostate cancer.

Meat and High-Temperature Cooking. Some evidence suggests that a high intake of red meat raises the risk for prostate cancer. Because red meat is high in saturated fat, such findings may explain the inconsistencies found in studies that simply look at fat content as a risk for prostate cancer. 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.

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 trace mineral 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.
• Cruciferous vegetables (cauliflower and broccoli) have cancer-fighting chemicals.
• Boron-rich foods (nuts, red grapes, avocados, and dried fruits) may also be protective.
• Green tea. Scientists have speculated that the antioxidants contained in green tea may help to inhibit prostate cancer growth. Investigators are researching the effects of both green tea and green tea extract supplements, but results to date have been inconclusive.

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.

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 affects 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 D. Vitamin D may help protect against prostate cancer. Some studies suggest that higher blood levels of vitamin D are associated with a lower risk of prostate cancer. Men should make sure they are getting enough vitamin D through sunlight exposure, food, or vitamin 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.

The National Cancer Institute is conducting a large-scale clinical trial of more than 35,000 men to investigate whether selenium, vitamin E, or a combination of these two dietary supplements can help to prevent prostate cancer. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is the largest prostate cancer prevention trial ever initiated.

Zinc. Zinc is of interest because it accumulates to the highest levels in a man's 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

Alcohol consumption does not appear to be associated with increased prostate cancer risk. A recent study, however, suggested a linear trend between red wine consumption and reduced risk of prostate cancer. In a study of over 1400 newly diagnosed middle-aged prostate cancer patients and matched controls, researchers found that each additional glass of red wine consumed per week reduced the relative risk of prostate cancer by 6%. Researchers theorize that the flavonoids contained in red wine may inhibit tumor cell growth. More research is needed to confirm these results.

Exercise

Regular physical activity may help reduce the risk of prostate cancer and slow the progression of the disease. The beneficial effects of exercise may be particularly important for older men. A 2006 study found that men ages 65 and older who exercised vigorously for at least 3 hours weekly had a 70% lower risk of being diagnosed with advanced prostate cancer.

Finasteride (Proscar)

Finasteride (Proscar) is a drug used to shrink the prostate in men with benign prostatic hyperplasia (BPH). It blocks an enzyme that converts testosterone to dehydroepiandrosterone (DHEA), the form of the male hormone that stimulates the prostate. Researchers are investigating whether finasteride may help prevent prostate cancer. In the 2003 Prostate Cancer Prevention Trial (PCPT), more than 18,000 men were randomly assigned to receive either finasteride or placebo. The men took the pills daily for 7 years. Results, published in 2003 in the New England Journal of Medicine, indicated that men who took finasteride were 25% less likely to develop prostate cancer than men who took placebo. However, although the finasteride group had less prostate cancers overall, those which did develop were higher-grade and more aggressive. Men who took finasteride had more sexual problems, including episodes of erectile dysfunction, but were less likely to have urinary problems such as incontinence. It is still unclear if finasteride is an appropriate preventive approach.

Sexual Activity

Frequent ejaculations from masturbation or sexual activity have 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. 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.