Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study
Dimitrakopoulou VI, Tsilidis KK, Haycock PC, Dimou NL, Al-Dabhani K, Martin RM, Lewis SJ, Gunter MJ, Mondul A, Shui IM, Theodoratou E, Nimptsch K, Lindström S, Albanes D, Kühn T, Key TJ, Travis RC, Vimaleswaran KS, GECCO Consortium, PRACTICAL Consortium, GAME-ON Network (CORECT, DRIVE, ELLIPSE, FOCI-OCAC, TRICL-ILCCO), Kraft P, Pierce BL, Schildkraut JM
BMJ (Clinical research ed.) · 130 citas
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Publicación
- Publicado
- 2017-10-31 · BMJ · vol. 359 · pág. j4761
- Citado
- 169 citas · más que el 99% de estudios similares · 14.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 66 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY
- Áreas de investigación
- Vitamin D Research Studies · Genetic Associations and Epidemiology · Nutrition, Genetics, and Disease
- Palabras clave
- vitamin D, 25-hydroxyvitamin D, cancer risk, colorectal cancer, breast cancer, prostate cancer, lung cancer, ovarian cancer, pancreatic cancer, neuroblastoma, single nucleotide polymorphisms, causal relationship, tumor subtypes
- MeSH
- humans, neoplasms, neuroblastoma, breast neoplasms, colorectal neoplasms, pancreatic neoplasms, ovarian neoplasms, lung neoplasms, prostatic neoplasms, vitamin d deficiency, genetic predisposition to disease, vitamin d, incidence, risk assessment, case-control studies, polymorphism, single nucleotide, female, male, genetic variation, genome-wide association study, mendelian randomization analysis
22 autores
- Vasiliki Dimitrakopoulou🇮🇪🇬🇷University College Dublin; University of Ioannina
- Konstantinos K. Tsilidis🇬🇷🇬🇧 · autor de correspondenciaUniversity of Ioannina; Imperial College London
- Philip Haycock🇬🇧University of Bristol; MRC Integrative Epidemiology Unit
- Niki L. Dimou🇬🇷University of Ioannina
- Kawthar M. Al-Dabhani🇬🇧Imperial College London
- Richard Michael Martin🇬🇧University Hospitals Bristol NHS Foundation Trust; University of Bristol
- Sarah J. Lewis🇬🇧University of Bristol; MRC Integrative Epidemiology Unit
- Marc James Gunter🇫🇷Centre international de recherche sur le cancer
- Alison M. Mondul🇺🇸University of Michigan
- Irene M. Shui🇺🇸Harvard University
- Evropi Τheodoratou🇬🇧University of Edinburgh
- Katharina Nimptsch🇩🇪Max Delbrück Center
- Sara Lindström🇺🇸University of Washington
- Demetrius Albanes🇺🇸National Cancer Institute; Division of Cancer Epidemiology and Genetics
- Tilman E. Kuhn🇩🇪German Cancer Research Center
- Timothy J. Key🇬🇧University of Oxford
- Ruth C. Travis🇬🇧University of Oxford
- Karani Santhanakrishnan Vimaleswaran🇬🇧University of Reading
- the GAME-ON Network (CORECT, DRIVE, ELLIPSE, FOCI-OCAC, TRICL-ILCCO)🇺🇸Harvard University
- Peter Kraft🇺🇸Harvard University; University of Chicago
- Brandon L. Pierce🇺🇸University of Chicago; University of Virginia
- Joellen M. Schildkraut🇺🇸University of Virginia
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objective 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.
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