Circulating selenium and prostate cancer risk: A mendelian randomization analysis

James Yarmolinsky, Carolina Bonilla, Philip Haycock, Ryan Langdon, Luca A Lotta, Claudia Langenberg, Caroline Relton, Sarah Lewis, David Evans, George Davey Smith, Richard Martin*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

23 Citations (Scopus)
263 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1035-1038
Number of pages4
JournalJournal of the National Cancer Institute
Volume110
Issue number9
Early online date17 May 2018
DOIs
Publication statusPublished - Sep 2018

Structured keywords

  • ICEP

Keywords

  • vitamin e
  • Selenium
  • Diabetes Mellitus
  • TYPE 2
  • Single Nucleotide Polymorphism
  • Proxy
  • EPIDEMIOLOGIC CAUSALITY
  • genetics
  • prosatate cancer
  • cancer prevention
  • genome - wide association study
  • prevention
  • Mendelian randomisation analysis

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