Circulating selenium and prostate cancer risk: A mendelian randomization analysis

Abstract

In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing amedian 114 lg/L increase in circulating selenium) did not lower overall prostate cancer risk, but increased risk of high-grade prostate cancer and type 2 diabetes. Mendelian randomization analysis uses genetic variants to proxymodifiable risk factors and can strengthen causal inference in observational studies.We constructed a genetic instrument comprising 11 single nucleotide polymorphisms robustly (P < 510-8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72 729men in the PRACTICAL Consortium (44 825 case subjects, 27 904 control subjects), 114 lg/L higher genetically elevated circulating selenium was not associated with prostate cancer (odds ratio [OR] 1.01, 95% confidence interval [CI] 0.89 to 1.13). In concordance with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR 1.21, 95% CI 0.98 to 1.49) and type 2 diabetes (OR 1.18, 95% CI 0.97 to 1.43; in a type 2 diabetes genome-wide association study meta-analysis with up to 49 266 case subjects and 249 906 control subjects). Our Mendelian randomization analyses do not support a role for seleniumsupplementation in prostate cancer prevention and suggest that supplementation could have adverse effects on risks of advanced prostate cancer and type 2 diabetes.