Fact Sheets - Endometriosis

Issue: Human exposure to hormonally active chemicals is contributing to the rise in prostate cancer rates.

Background: Prostate cancer is an androgen-dependent disease that is rare before age 50 years, incidence rates increasing steeply at older ages. The lifetime risk of developing prostate cancer is estimated to be 11% and the likelihood of dying from this disease is 3.6%. There will be an estimated 189,000 new cases and 30,200 deaths from prostate cancer in United States during 2002. Prostate cancer incidence and mortality rates among U.S. Blacks are the highest in the world. As assessed by studies of familial clusters, genetic factors alone likely explain less than 10% of prostate cancers.

Disease trends: Prostate cancer incidence rates have increased substantially in several countries since about 1970. Introduction and widespread use of the PSA (prostate-specific antigen) blood test that enables early prostate cancer detection is thought to account for sharply increased prostate cancer incidence rates observed during the late 1980's. Prostate cancer death rates also increased after 1970 but less dramatically than incidence rates. Both incidence and mortality rates appear to have declined slightly during the past few years. Moreover, it is now clear that there are at least two forms of the disease, a slow growing cancer that remains in the prostate gland which is very common and a rapidly-growing, metastasizing form that causes clinically-relevant prostate cancer. The relationship between these two forms of the disease is not clear. The reasons for prostate cancer increases before the late 1980's may have included both a true increased risk and improved diagnosis because of safer surgical procedures and a more aggressive approach toward treatment of older men.

Consistency of the data: Most prostate cancers are dependent on male hormones (androgens) that bind to androgen receptors in prostate cells and stimulate their growth and function. Anti-androgen drugs have been use to treat benign and malignant prostate disease and are being tested for ability to prevent prostate cancer. There is preliminary evidence that altered male hormone balance may increase prostate cancer risk. This raises the possibility that mutations in the AR gene or exposure to environmental chemicals with hormonally active chemicals could modulate prostate cancer risk; for instance, recent evidence suggests that the elevated risk among U.S. Blacks may be caused in part by racial differences in AR gene polymorphisms. Increased prostate cancer risks have also been linked to polymorphisms in CYP17 and GSTP I, genes that encode enzymes that can activate or inactivate environmental carcinogens.

No strong external risk factors have been identified for prostate cancer. Most known or suspected risk factors could act through hormonal mechanisms but direct evidence is generally lacking; they could also act through non-hormonal mechanisms such as genotoxicity. There is limited, often inconsistent epidemiologic evidence for dietary factors that may reduce (vegetables, fruits, tomato products, cabbage, brussels sprouts, cauliflower, beans, peanuts, soy foods, selenium, vitamin E, beta-carotene, lycopenes) or increase (animal fat, red meats, dairy products, calcium, cured meat) the risk of prostate cancer. Five cohort studies of vegetarians, however, showed no reduction of prostate cancer risks. Diets high in fat and simple carbohydrates tend to raise insulin and insulin-like growth factor levels; the latter promote increased sex steroid synthesis, stimulate cell proliferation and have been linked to increased prostate cancer risks. Occupational exposures linked to increased risk of prostate cancer include: farming, pesticides, metal fabricating, and activities involving exposure to metallic dusts, cutting oils, and paints/varnishes. Evidence linking smoking to incident prostate cancer is mixed but risk was increased 2-3 times among men with high body mass index who started smoking before age 20 years or were heavy smokers. There is mixed evidence of a role for alcohol consumption in prostate cancer.

Experimental evidence: Prostatic hypertrophy has been demonstrated in various rodent experiments following treatment with estrogenic chemicals. These effects have been shown to occur at low concentrations. However, it should be noted that, although similar experimental protocols have been followed, other investigators have been unable to reproduce these findings. Moreover, even though the dose levels are considered to be low relative to the concentrations necessary to induce other adverse effects with these toxicants, the concentrations still considerably exceed the concentrations present in low dose birth control pills and thus these changes may not necessarily be considered low dose effects.

Changes in prostate gland growth in rodents have been suggested to indicate that similar changes may occur in humans. However, the extent to which chemical effects on rodent prostate gland development can be used to predicting risk of human prostate cancer is not clear, given the differences in gland anatomy and the fact that few rodents spontaneously develop prostate cancer. Furthermore, the mechanism of environmental contaminant induced changes in prostate gland differentiation and growth have yet to be elucidated.

Biological plausibility: In the absence of direct human evidence (demonstrated exposure, association between exposure and increased risk of prostate cancer, and evidence of contaminant induced changes in circulating levels of sex steroids of affected men compared to a reference population), there remains the theoretical possibility that hormonally active chemicals may modulate prostate cancer risk by altering sex steroid balance in men. However, the hypothesis that human exposure to hormonally active environmental chemicals is associated with an increased risk for the development of prostate cancer remains to be tested.

Conclusion: Despite much research, the main proven risk factors for prostate cancer risk are non-modifiable: age, family history, and race. Epidemiologic research on potential modifiable risk factors has shown associations with diet, occupation, lifestyle and other factors. At present, the inconsistencies and inadequacies of existing studies do not permit a conclusion that hormonally active chemicals are potential causative factors in prostate cancer.

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