Role of Hormonal and Other Factors in Human Prostate Cancer

Abstract American men have a lifetime risk of about 18% for prostate cancer diagnosis. Large international variations in prostate cancer risks and increased risks among migrants from low- to high-risk countries indicate important roles for environmental factors. Major known risk factors include age, family history and country/ethnicity. Type 2 diabetes appears to reduce risk while high birth weight and adult height are linked to increased risk of aggressive prostate cancer. Limited evidence supports an association with a history of sexually transmitted infections. A meta-analysis of 8 cohort studies indicated no associations with plasma androgen, estrogen or sex hormone binding globulin (SHBG) levels. However, there were dose-response relationships with baseline plasma testosterone levels in 2 studies that adjusted for other serum hormones and obesity. Finasteride (a drug that blocks testosterone activation) reduced prostate cancer risk by 25%. Low-frequency genes linked to familial prostate cancer only explain a small fraction of all cases. Sporadic cases were linked to relatively common polymorphisms of genes involved in (1) androgen synthesis, activation, inactivation and excretion, (2) hormone and vitamin D receptors, (3) carcinogen metabolism and (4) DNA repair. Epidemiologic evidence supports protective roles for dietary selenium, vitamin E, pulses, tomatoes/lycopene and soy foods and high plasma 1,25-dihydroxyvitamin D levels. There is inadequate evidence that vegetables, fruit, carotenoids and vitamins A and C reduce risk and that animal fat, α-linoleic acid, meat, coffee and tea increase risk. Two major cohort studies found dose-response relationships with dietary calcium intake. Total dietary energy intake may enhance risk. Limited evidence supports a protective role for !4 !5 physical activity and elevated risk for farmers and other men with occupational pesticide exposure, particularly organochlorine compounds and phenoxy herbicides. There is inadequate evidence for a relationship with alcohol or smoking. Most known or suspected external risk factors may act through hormonal mechanisms but our review found little supporting evidence and substantial further research is needed.