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dc.contributor.authorJiang, X
dc.contributor.authorDimou, NL
dc.contributor.authorAl-Dabhani, K
dc.contributor.authorLewis, SJ
dc.contributor.authorMartin, RM
dc.contributor.authorHaycock, PC
dc.contributor.authorGunter, MJ
dc.contributor.authorKey, TJ
dc.contributor.authorEeles, RA
dc.contributor.authorMuir, K
dc.contributor.authorNeal, D
dc.contributor.authorGiles, GG
dc.contributor.authorGiovannucci, EL
dc.contributor.authorStampfer, M
dc.contributor.authorPierce, BL
dc.contributor.authorSchildkraut, JM
dc.contributor.authorWarren Andersen, S
dc.contributor.authorThompson, D
dc.contributor.authorZheng, W
dc.contributor.authorKraft, P
dc.contributor.authorTsilidis, KK
dc.contributor.authorPRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia
dc.date.accessioned2019-02-20T11:38:01Z
dc.date.issued2019-10
dc.identifier.citationInternational journal of epidemiology, 2019, 48 (5), pp. 1416 - 1424
dc.identifier.issn0300-5771
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3076
dc.identifier.eissn1464-3685
dc.identifier.doi10.1093/ije/dyy284
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.
dc.formatPrint
dc.format.extent1416 - 1424
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectPRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectProstatic Neoplasms
dc.subjectVitamin D
dc.subjectReceptors, Estrogen
dc.subjectRisk Factors
dc.subjectCausality
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.subjectMendelian Randomization Analysis
dc.titleCirculating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study.
dc.typeJournal Article
dcterms.dateAccepted2018-12-06
rioxxterms.versionofrecord10.1093/ije/dyy284
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2019-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfInternational journal of epidemiology
pubs.issue5
pubs.notes12 months
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.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
pubs.volume48
pubs.embargo.terms12 months
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden


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