Abstract and Introduction
Background. The Selenium and Vitamin E Cancer Prevention Trial found no effect of selenium supplementation on prostate cancer (PCa) risk but a 17% increased risk from vitamin E supplementation. This case–cohort study investigates effects of selenium and vitamin E supplementation conditional upon baseline selenium status.
Methods. There were 1739 total and 489 high-grade (Gleason 7–10) PCa cases and 3117 men in the randomly selected cohort. Proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effects of supplementation within quintiles of baseline toenail selenium. Cox proportional hazards models were used to estimate hazard ratios, and all statistical tests are two-sided.
Results. Toenail selenium, in the absence of supplementation, was not associated with PCa risk. Selenium supplementation (combined selenium only and selenium + vitamin E arms) had no effect among men with low selenium status (<60th percentile of toenail selenium) but increased the risk of high-grade PCa among men with higher selenium status by 91% (P = .007). Vitamin E supplementation (alone) had no effect among men with high selenium status (≥40th percentile of toenail selenium) but increased the risks of total, low-grade, and high-grade PCa among men with lower selenium status (63%, P = .02; 46%, P = .09; 111%, P = .008, respectively).
Conclusions. Selenium supplementation did not benefit men with low selenium status but increased the risk of high-grade PCa among men with high selenium status. Vitamin E increased the risk of PCa among men with low selenium status. Men should avoid selenium or vitamin E supplementation at doses that exceed recommended dietary intakes.
In 2001, the US National Cancer Institute initiated the Selenium and Vitamin E Cancer Prevention Trial (SELECT), which tested whether selenium (Se; 200 μg/d from L-selenomethionine), vitamin E (400 IU/d of all rac-α-tocopheryl acetate) or both could reduce prostate cancer (PCa) risk. Study supplementation stopped 3 years before the expected trial end date because interim analyses showed very low likelihood of benefit with continued intervention. At that time, vitamin E alone modestly increased PCa risk (hazard ratio [HR] = 1.13; P < .06); with additional follow-up, this became statistically significant (HR = 1.17; P < .008).
Here we examine two prespecified hypotheses related to baseline Se status and SELECT outcomes. First, we tested whether high Se status at baseline was associated with reduced cancer risk among men receiving placebo supplements, which addresses whether Se exposure within ranges common among US men was associated with risk. Second, we tested whether Se supplementation reduced cancer risk among men with low Se status at baseline. This was motivated by the Nutritional Prevention of Cancer Trial (NPC), which found that supplementation of men with moderate and low plasma Se decreased PCa risk by more than 75% but had no effect among men with high plasma Se. We also tested the a posteriori hypothesis that vitamin E supplementation increased PCa risk among men with low Se status at baseline, which was motivated by the finding that vitamin E alone, but not combined vitamin E and Se, increased cancer risk.
J Natl Cancer Inst. 2014;106(3) © 2014 Oxford University Press