A randomized, controlled chemoprevention trial of selenium in familial prostate cancer: Rationale, recruitment, and design issues

Deficiencies of selenium have been associated with an increased cancer risk , and several clinical and animal trials have suggested that improved selen ium nutrition may reduce the incidence of several kinds of cancer, includin g lung, colorectal, and breast. Results from recent trials also show atl an ticarcinogenic effect of selenium in the prostate. There is converging evid ence from epidemiologic, experimental animal, and molecular biology studies for an antitumor effect of selenium. Evidence suggests there are two modes of action of selenium affecting cancer risk: first, by functioning as an e ssential nutrient that provides the catalytic centers of a number of seleno enzymes, including some with antioxidant and redox functions; second, by se rving as a source of selenium metabolytes that affect carcinogenesis in oth er ways. The first mechanism appears most relevant to protection against ca ncer initiation, the second against cancer progression. There is conclusive evidence of the increased risk of prostate cancer for a male with a family history of the disease. As a result of this evidence, and the evidence sup porting the chemopreventive properties of selenium, this study proposed tha t a trial to test the effect of selenium on men at high risk for developmen t of prostate cancer is appropriate. This article describes the Australian Prostate Cancer Prevention Trial Using Selenium (APPOSE) trial to test the hypothesis that daily dietary supplementation with selenium will reduce pro state cancer incidence in a population of men who are at increased risk bec ause of a first-degree relative with prostate cancer.