dc.contributor.author | Jiang, X | |
dc.contributor.author | Dimou, NL | |
dc.contributor.author | Al-Dabhani, K | |
dc.contributor.author | Lewis, SJ | |
dc.contributor.author | Martin, RM | |
dc.contributor.author | Haycock, PC | |
dc.contributor.author | Gunter, MJ | |
dc.contributor.author | Key, TJ | |
dc.contributor.author | Eeles, RA | |
dc.contributor.author | Muir, K | |
dc.contributor.author | Neal, D | |
dc.contributor.author | Giles, GG | |
dc.contributor.author | Giovannucci, EL | |
dc.contributor.author | Stampfer, M | |
dc.contributor.author | Pierce, BL | |
dc.contributor.author | Schildkraut, JM | |
dc.contributor.author | Warren Andersen, S | |
dc.contributor.author | Thompson, D | |
dc.contributor.author | Zheng, W | |
dc.contributor.author | Kraft, P | |
dc.contributor.author | Tsilidis, KK | |
dc.contributor.author | PRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia, | |
dc.date.accessioned | 2019-02-20T11:38:01Z | |
dc.date.issued | 2019-10-01 | |
dc.identifier.citation | International journal of epidemiology, 2019, 48 (5), pp. 1416 - 1424 | |
dc.identifier.issn | 0300-5771 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3076 | |
dc.identifier.eissn | 1464-3685 | |
dc.identifier.doi | 10.1093/ije/dyy284 | |
dc.description.abstract | BACKGROUND: 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.format | Print | |
dc.format.extent | 1416 - 1424 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | OXFORD UNIV PRESS | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | PRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Prostatic Neoplasms | |
dc.subject | Vitamin D | |
dc.subject | Receptors, Estrogen | |
dc.subject | Risk Factors | |
dc.subject | Causality | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Genome-Wide Association Study | |
dc.subject | Mendelian Randomization Analysis | |
dc.title | Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-12-06 | |
rioxxterms.versionofrecord | 10.1093/ije/dyy284 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2019-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | International journal of epidemiology | |
pubs.issue | 5 | |
pubs.notes | 12 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-status | Published | |
pubs.volume | 48 | |
pubs.embargo.terms | 12 months | |
icr.researchteam | Oncogenetics | |
dc.contributor.icrauthor | Eeles, Rosalind | |