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Publication - Mr James Yarmolinsky

    Circulating selenium and prostate cancer risk

    A mendelian randomization analysis

    Citation

    Yarmolinsky, J, Bonilla, C, Haycock, P, Langdon, R, Lotta, LA, Langenberg, C, Relton, C, Lewis, S, Evans, D, Smith, GD & Martin, R, 2018, ‘Circulating selenium and prostate cancer risk: A mendelian randomization analysis’. Journal of the National Cancer Institute, vol 110., pp. 1035-1038

    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.

    Full details in the University publications repository