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bioRxiv · 10.1101/223248

Circulating selenium and prostate cancer risk: a Mendelian randomization analysis

Yarmolinsky, J.·Bonilla, C.·Haycock, P. C.·Langdon, R. J.·Lotta, L. A.·Langenberg, C.·Relton, C. L.·Lewis, S. J.·Evans, D. M.·the PRACTICAL consortium,·Smith, G. D.·Martin, R. M.
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Abstract

In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 g/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 proxy modifiable risk factors and can strengthen causal inference in observational studies. We constructed a genetic risk score comprising eleven single-nucleotide polymorphisms robustly (P<5x10-8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72,729 men in the PRACTICAL Consortium (44,825 cases, 27,904 controls), 114 g/L higher genetically-elevated circulating selenium was not associated with prostate cancer (OR: 1.01; 95% CI: 0.89-1.13). Concordant with findings from SELECT, selenium was weakly associated with advanced (including high-grade) prostate cancer (OR: 1.21; 95% CI: 0.98-1.49) and type 2 diabetes (OR: 1.18; 95% CI: 0.97-1.43; in a type 2 diabetes GWAS meta-analysis with up to 49,266 cases, 249,906 controls). Mendelian randomization mirrored the outcome of selenium supplementation in SELECT and may offer an approach for the prioritization of interventions for follow-up in large-scale randomized controlled trials.

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Yarmolinsky, J., Bonilla, C., Haycock, P. C., Langdon, R. J., Lotta, L. A., Langenberg, C., Relton, C. L., Lewis, S. J., Evans, D. M., the PRACTICAL consortium,, Smith, G. D., Martin, R. M.. 2017-11-21. Circulating selenium and prostate cancer risk: a Mendelian randomization analysis. https://doi.org/10.1101/223248

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