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dc.contributor.authorDimitrakopoulou, VIen_US
dc.contributor.authorTsilidis, KKen_US
dc.contributor.authorHaycock, PCen_US
dc.contributor.authorDimou, NLen_US
dc.contributor.authorAl-Dabhani, Ken_US
dc.contributor.authorMartin, RMen_US
dc.contributor.authorLewis, SJen_US
dc.contributor.authorGunter, MJen_US
dc.contributor.authorMondul, Aen_US
dc.contributor.authorShui, IMen_US
dc.contributor.authorTheodoratou, Een_US
dc.contributor.authorNimptsch, Ken_US
dc.contributor.authorLindström, Sen_US
dc.contributor.authorAlbanes, Den_US
dc.contributor.authorKühn, Ten_US
dc.contributor.authorKey, TJen_US
dc.contributor.authorTravis, RCen_US
dc.contributor.authorVimaleswaran, KSen_US
dc.contributor.authorGECCO Consortiumen_US
dc.contributor.authorPRACTICAL Consortiumen_US
dc.contributor.authorGAME-ON Network (CORECT, DRIVE, ELLIPSE, FOCI-OCAC, TRICL-ILCCO)en_US
dc.contributor.authorKraft, Pen_US
dc.contributor.authorPierce, BLen_US
dc.contributor.authorSchildkraut, JMen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2019-02-20T11:41:58Z
dc.date.issued2017-10-31en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29089348en_US
dc.identifier.citationBMJ, 2017, 359 pp. j4761 - ?en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3077
dc.identifier.eissn1756-1833en_US
dc.identifier.doi10.1136/bmj.j4761en_US
dc.description.abstractObjective To determine if circulating concentrations of vitamin D are causally associated with risk of cancer.Design Mendelian randomisation study.Setting Large genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAME-ON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform).Participants 70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls.Exposures Four single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to define a multi-polymorphism score for circulating 25-hydroxyvitamin D (25(OH)D) concentrations.Main outcomes measures The primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specific polymorphisms and a likelihood based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined.Results There was little evidence that the multi-polymorphism score of 25(OH)D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically determined 25(OH)D concentrations were 0.92 (95% confidence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89 (0.77 to 1.02) for prostate cancer, and 1.03 (0.87 to 1.23) for lung cancer. The results were consistent with the two different analytical approaches, and the study was powered to detect relative effect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH)D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated.Conclusions There is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant effects of low magnitude cannot be ruled out. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention.en_US
dc.format.extentj4761 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectBreast Neoplasmsen_US
dc.subjectCase-Control Studiesen_US
dc.subjectColorectal Neoplasmsen_US
dc.subjectFemaleen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectGenetic Variationen_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectHumansen_US
dc.subjectIncidenceen_US
dc.subjectLung Neoplasmsen_US
dc.subjectMaleen_US
dc.subjectMendelian Randomization Analysisen_US
dc.subjectNeoplasmsen_US
dc.subjectNeuroblastomaen_US
dc.subjectOvarian Neoplasmsen_US
dc.subjectPancreatic Neoplasmsen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectProstatic Neoplasmsen_US
dc.subjectRisk Assessmenten_US
dc.subjectVitamin Den_US
dc.subjectVitamin D Deficiencyen_US
dc.titleCirculating vitamin D concentration and risk of seven cancers: Mendelian randomisation study.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-09-26en_US
rioxxterms.versionofrecord10.1136/bmj.j4761en_US
rioxxterms.licenseref.startdate2017-10-31en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBMJen_US
pubs.notesNot knownen_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.volume359en_US
pubs.embargo.termsNot knownen_US
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden_US


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