In the vitamin E group, the risk of prostate cancer generally decreased with each additional quintile of alpha-tocopherol at baseline. In contrast, within the selenium and combination groups, the risk increased with quintile, and within the placebo group, risk was unaffected.
The results were "somewhat opposite" for plasma gamma-tocopherol levels at baseline. In the vitamin E group, the risk generally increased with quintile. In contrast, within all the other groups, the risk decreased with quintile.
The findings have noteworthy implications for the design of clinical trials, said Dr. Klein.
"There were interactions between selenium and vitamin E with respect to risk, and a factorial design would not have captured that. So it’s important that these be powered to allow for these interactions to be tested for," he explained. "And maybe most importantly, for agents whose biology we don’t really understand and don’t really understand what the time line of the effect is, that postintervention follow-up is critical: If we had not continued to follow these men beyond the 5.5 years that they took the supplements, we would not have discovered [the elevated risk with vitamin E]".
Dr. Klein disclosed that he had no relevant conflicts of interest.