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dc.contributor.authorJiang, Xen_US
dc.contributor.authorDimou, NLen_US
dc.contributor.authorAl-Dabhani, Ken_US
dc.contributor.authorLewis, SJen_US
dc.contributor.authorMartin, RMen_US
dc.contributor.authorHaycock, PCen_US
dc.contributor.authorGunter, MJen_US
dc.contributor.authorKey, TJen_US
dc.contributor.authorEeles, RAen_US
dc.contributor.authorMuir, Ken_US
dc.contributor.authorNeal, Den_US
dc.contributor.authorGiles, GGen_US
dc.contributor.authorGiovannucci, ELen_US
dc.contributor.authorStampfer, Men_US
dc.contributor.authorPierce, BLen_US
dc.contributor.authorSchildkraut, JMen_US
dc.contributor.authorWarren Andersen, Sen_US
dc.contributor.authorThompson, Den_US
dc.contributor.authorZheng, Wen_US
dc.contributor.authorKraft, Pen_US
dc.contributor.authorTsilidis, KKen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2019-02-20T11:38:01Z
dc.date.issued2018-12-28en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30597039en_US
dc.identifier5265299en_US
dc.identifier.citationInt J Epidemiol, 2018en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3076
dc.identifier.eissn1464-3685en_US
dc.identifier.doi10.1093/ije/dyy284en_US
dc.description.abstractBackground: Observational studies have suggested an association between circulating vitamin D concentrations [25(OH)D] and risk of breast and prostate cancer, which was not supported by a recent Mendelian randomization (MR) analysis comprising 15 748 breast and 22 898 prostate-cancer cases. Demonstrating causality has proven challenging and one common limitation of MR studies is insufficient power. Methods: We aimed to determine whether circulating concentrations of vitamin D are causally associated with the risk of breast and prostate cancer, by using summary-level data from the largest ever genome-wide association studies conducted on vitamin D (N = 73 699), breast cancer (Ncase = 122 977) and prostate cancer (Ncase = 79 148). We constructed a stronger instrument using six common genetic variants (compared with the previous four variants) and applied several two-sample MR methods. Results: We found no evidence to support a causal association between 25(OH)D and risk of breast cancer [OR per 25 nmol/L increase, 1.02 (95% confidence interval: 0.97-1.08), P = 0.47], oestrogen receptor (ER)+ [1.00 (0.94-1.07), P = 0.99] or ER- [1.02 (0.90-1.16), P = 0.75] subsets, prostate cancer [1.00 (0.93-1.07), P = 0.99] or the advanced subtype [1.02 (0.90-1.16), P = 0.72] using the inverse-variance-weighted method. Sensitivity analyses did not reveal any sign of directional pleiotropy. Conclusions: Despite its almost five-fold augmented sample size and substantially improved statistical power, our MR analysis does not support a causal effect of circulating 25(OH)D concentrations on breast- or prostate-cancer risk. However, we can still not exclude a modest or non-linear effect of vitamin D. Future studies may be designed to understand the effect of vitamin D in subpopulations with a profound deficiency.en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.titleCirculating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-12-06en_US
rioxxterms.versionofrecord10.1093/ije/dyy284en_US
rioxxterms.licenseref.startdate2018-12-28en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfInt J Epidemiolen_US
pubs.notes12 monthsen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.publication-statusPublished onlineen_US
pubs.embargo.terms12 monthsen_US
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden_US


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