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Selenium and cancer risk: Wide-angled Mendelian randomization analysis.

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cam.issuedOnline2021-12-24
dc.contributor.authorYuan, Shuai
dc.contributor.authorMason, Amy M
dc.contributor.authorCarter, Paul
dc.contributor.authorVithayathil, Mathew
dc.contributor.authorKar, Siddhartha
dc.contributor.authorBurgess, Stephen
dc.contributor.authorLarsson, Susanna C
dc.contributor.orcidYuan, Shuai [0000-0001-5055-5627]
dc.contributor.orcidLarsson, Susanna C [0000-0003-0118-0341]
dc.date.accessioned2022-01-06T11:49:42Z
dc.date.available2022-01-06T11:49:42Z
dc.date.issued2022-04-01
dc.date.submitted2021-09-15
dc.date.updated2022-01-06T11:49:42Z
dc.descriptionFunder: Swedish Cancer Society (Cancerfonden); Id: http://dx.doi.org/10.13039/501100002794
dc.descriptionFunder: EC‐Innovative Medicines Initiative (BigData@Heart)
dc.description.abstractEvidence on the association between selenium and cancer risk is inconclusive. We conducted a Mendelian randomization study to examine the associations of selenium levels with 22 site-specific cancers and any cancer. Single nucleotide polymorphisms (SNPs) strongly associated with toenail and blood (TAB) and blood selenium levels in mild linkage disequilibrium (r2  < .3) were used as instrumental variables. Genetic associations of selenium-associated SNPs with cancer were obtained from the UK Biobank including a total of 59 647 cancer cases and 307 914 controls. Associations with P < .1 in UK Biobank were tested for replication in the FinnGen consortium comprising more than 180 000 individuals. The inverse-variance weighted method accounting for linkage disequilibrium was used to estimate the associations. Genetically predicted TAB selenium levels were not associated with the risk of the 22 site-specific cancers or any cancer (all 22 site-specific cancers). Similarly, we observed no strong association for genetically predicted blood selenium levels. However, genetically predicted blood selenium levels showed suggestive associations with risk of kidney cancer (odds ratio [OR] per one-unit increase in log-transformed levels: 0.83; 95% confidence interval [CI]: 0.67-1.03) and multiple myeloma (OR: 1.40; 95% CI: 1.02-1.93). The same direction of association for kidney cancer but not for multiple myeloma was observed in FinnGen. In the metaanalysis of UK Biobank and FinnGen, the OR of kidney cancer was 0.83 (95% CI: 0.69-1.00). Our study suggests that high selenium status may not prevent cancer development. The associations for kidney cancer and multiple myeloma need to be verified in well-powered studies.
dc.identifier.doi10.17863/CAM.79590
dc.identifier.eissn1097-0215
dc.identifier.issn0020-7136
dc.identifier.otherijc33902
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332144
dc.languageen
dc.language.isoeng
dc.publisherWiley
dc.publisher.urlhttp://dx.doi.org/10.1002/ijc.33902
dc.subjectMendelian randomization
dc.subjectcancer
dc.subjectkidney cancer
dc.subjectselenium
dc.subjectHumans
dc.subjectKidney Neoplasms
dc.subjectMendelian Randomization Analysis
dc.subjectMultiple Myeloma
dc.subjectNails
dc.subjectPolymorphism, Single Nucleotide
dc.subjectSelenium
dc.titleSelenium and cancer risk: Wide-angled Mendelian randomization analysis.
dc.typeArticle
dcterms.dateAccepted2021-12-01
prism.publicationNameInt J Cancer
pubs.funder-project-idWellcome Trust (204623/Z/16/Z)
pubs.funder-project-idNational Institute for Health and Care Research (IS-BRC-1215-20014)
pubs.funder-project-idBritish Heart Foundation (None)
pubs.funder-project-idBritish Heart Foundation (CH/12/2/29428)
pubs.funder-project-idBritish Heart Foundation (RG/18/13/33946)
pubs.funder-project-idMedical Research Council (MC_UU_00002/7)
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1002/ijc.33902

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