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dc.contributor.authorDimitrakopoulou, VI
dc.contributor.authorTsilidis, KK
dc.contributor.authorHaycock, PC
dc.contributor.authorDimou, NL
dc.contributor.authorAl-Dabhani, K
dc.contributor.authorMartin, RM
dc.contributor.authorLewis, SJ
dc.contributor.authorGunter, MJ
dc.contributor.authorMondul, A
dc.contributor.authorShui, IM
dc.contributor.authorTheodoratou, E
dc.contributor.authorNimptsch, K
dc.contributor.authorLindström, S
dc.contributor.authorAlbanes, D
dc.contributor.authorKühn, T
dc.contributor.authorKey, TJ
dc.contributor.authorTravis, RC
dc.contributor.authorVimaleswaran, KS
dc.contributor.authorGECCO Consortium
dc.contributor.authorPRACTICAL Consortium
dc.contributor.authorGAME-ON Network (CORECT, DRIVE, ELLIPSE, FOCI-OCAC, TRICL-ILCCO)
dc.contributor.authorKraft, P
dc.contributor.authorPierce, BL
dc.contributor.authorSchildkraut, JM
dc.date.accessioned2019-02-20T11:41:58Z
dc.date.issued2017-10-31
dc.identifier.citationBMJ (Clinical research ed.), 2017, 359 pp. j4761 - ?
dc.identifier.issn0959-8138
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3077
dc.identifier.eissn1756-1833
dc.identifier.doi10.1136/bmj.j4761
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.
dc.formatElectronic
dc.format.extentj4761 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectGECCO Consortium
dc.subjectPRACTICAL Consortium
dc.subjectGAME-ON Network (CORECT, DRIVE, ELLIPSE, FOCI-OCAC, TRICL-ILCCO)
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectNeuroblastoma
dc.subjectBreast Neoplasms
dc.subjectColorectal Neoplasms
dc.subjectPancreatic Neoplasms
dc.subjectOvarian Neoplasms
dc.subjectLung Neoplasms
dc.subjectProstatic Neoplasms
dc.subjectVitamin D Deficiency
dc.subjectGenetic Predisposition to Disease
dc.subjectVitamin D
dc.subjectIncidence
dc.subjectRisk Assessment
dc.subjectCase-Control Studies
dc.subjectPolymorphism, Single Nucleotide
dc.subjectFemale
dc.subjectMale
dc.subjectGenetic Variation
dc.subjectGenome-Wide Association Study
dc.subjectMendelian Randomization Analysis
dc.titleCirculating vitamin D concentration and risk of seven cancers: Mendelian randomisation study.
dc.typeJournal Article
dcterms.dateAccepted2017-09-26
rioxxterms.versionofrecord10.1136/bmj.j4761
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-10-31
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBMJ (Clinical research ed.)
pubs.declined2019-02-20T11:40:30.84+0000
pubs.notesNot known
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.volume359
pubs.embargo.termsNot known
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden


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