In 1996, a wave of hope arose when the Nutritional Prevention of Cancer trial reported a 65% reduction in prostate cancer incidence in men receiving selenium supplementation.1 This came only 2 years after the ATBC (α-Tocopherol, Beta Carotene) Cancer Prevention Trial had reported a 35% reduction in prostate cancer occurrence among men taking vitamin E supplements.2 Suddenly, it appeared to make sense that this cancer could be prevented by bolstering antioxidant defenses in middle-aged and older men. Prostate cancer was not a prespecified end point in either trial, and although both results were based on post hoc analysis, randomization had worked and it seemed unlikely that the encouraging findings were due to confounding bias. Indeed, confounding stood as the likely explanation for discordance between the earlier beta carotene trials that failed to demonstrate any benefit and numerous observational studies reporting that men who consumed beta carotene–containing foods were at lower risk for developing cancer, particularly those of the respiratory tract.
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