Circulating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis

• Published in: JNCI : Journal of the National Cancer Institute Vol. 110; no. 9; pp. 1035 - 1038
• Main Authors: Yarmolinsky, James, Bonilla, Carolina, Haycock, Philip C, Langdon, Ryan J Q, Lotta, Luca A, Langenberg, Claudia, Relton, Caroline L, Lewis, Sarah J, Evans, David M, Davey Smith, George, Martin, Richard M
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.09.2018
• Subjects: Brief Communications; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - etiology; Genetic Predisposition to Disease; Humans; Male; Mendelian Randomization Analysis; Odds Ratio; Polymorphism, Single Nucleotide; Prostatic Neoplasms - epidemiology; Prostatic Neoplasms - etiology; Prostatic Neoplasms - pathology; Risk Assessment; Risk Factors; Selenium - adverse effects; Selenium - blood
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/djy081

In the Selenium and Vitamin E Cancer Prevention Trial (SELECT), selenium supplementation (causing a median 114 μg/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 instrument comprising 11 single nucleotide polymorphisms robustly (P < 5 × 10-8) associated with circulating selenium in genome-wide association studies. In a Mendelian randomization analysis of 72 729 men in the PRACTICAL Consortium (44 825 case subjects, 27 904 control subjects), 114 μg/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 selenium supplementation in prostate cancer prevention and suggest that supplementation could have adverse effects on risks of advanced prostate cancer and type 2 diabetes.