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dc.contributor.authorYarmolinsky, Jamesen
dc.contributor.authorBonilla, Carolinaen
dc.contributor.authorHaycock, Philip Cen
dc.contributor.authorLangdon, Ryan JQen
dc.contributor.authorLotta, Lucaen
dc.contributor.authorLangenberg, Claudiaen
dc.contributor.authorRelton, Caroline Len
dc.contributor.authorLewis, Sarah Jen
dc.contributor.authorEvans, David Men
dc.contributor.authorPRACTICAL Consortium,en
dc.contributor.authorDavey Smith, Georgeen
dc.contributor.authorMartin, Richard Men
dc.date.accessioned2018-09-18T13:52:22Z
dc.date.available2018-09-18T13:52:22Z
dc.date.issued2018-09-01en
dc.identifier.issn0027-8874
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280326
dc.description.abstractIn 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.
dc.languageengen
dc.publisherOUP
dc.rightsAttribution 4.0 International
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectvitamin een
dc.subjectseleniumen
dc.subjectdiabetes mellitus, type 2en
dc.subjectsingle nucleotide polymorphismen
dc.subjectproxyen
dc.subjectepidemiologic causalityen
dc.subjectgeneticsen
dc.subjectprostate canceren
dc.subjectcancer preventionen
dc.subjectgenome-wide association studyen
dc.subjectpreventionen
dc.subjectmendelian randomization analysisen
dc.titleCirculating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis.en
dc.typeArticle
prism.endingPage1038
prism.issueIdentifier9en
prism.publicationDate2018en
prism.publicationNameJournal of the National Cancer Instituteen
prism.startingPage1035
prism.volume110en
dc.identifier.doi10.17863/CAM.27700
dcterms.dateAccepted2018-03-30en
rioxxterms.versionofrecord10.1093/jnci/djy081en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2018-09-01en
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.identifier.eissn1460-2105
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/1)
cam.issuedOnline2018-05-17en
dc.identifier.urlhttps://academic.oup.com/jnci/article/110/9/1035/4996958en


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International