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Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study.
BMJ. 2017 10 31; 359:j4761.BMJ

Abstract

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.

Authors+Show Affiliations

Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece. School of Mathematics and Statistics, University College Dublin, Dublin, Ireland.Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece ktsilidi@cc.uoi.gr. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.School of Social and Community Medicine, University of Bristol, Bristol, UK. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, Ioannina, Greece.Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.School of Social and Community Medicine, University of Bristol, Bristol, UK. National Institute for Health Research (NIHR) Bristol Nutritional Biomedical Research Unit, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK.School of Social and Community Medicine, University of Bristol, Bristol, UK. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.International Agency for Research on Cancer, Lyon, France.Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.Centre of Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburg, Edinburgh, UK.Molecular Epidemiology Research Group, Max Delbrück Centre for Molecular Medicine (MDC), Berlin, Germany.Department of Epidemiology, University of Washington, Seattle, WA, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.Division of Cancer Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.Department of Food and Nutritional Sciences, Hugh Sinclair Unit of Human Nutrition and Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, Reading, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableProgram in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.Department of Public Health Sciences, University of Chicago, Chicago, IL, USA. Department of Human Genetics, University of Chicago, Chicago, IL, USA.Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29089348

Citation

Dimitrakopoulou, Vasiliki I., et al. "Circulating Vitamin D Concentration and Risk of Seven Cancers: Mendelian Randomisation Study." BMJ (Clinical Research Ed.), vol. 359, 2017, pp. j4761.
Dimitrakopoulou VI, Tsilidis KK, Haycock PC, et al. Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study. BMJ. 2017;359:j4761.
Dimitrakopoulou, V. I., Tsilidis, K. K., Haycock, P. C., Dimou, N. L., Al-Dabhani, K., Martin, R. M., Lewis, S. J., Gunter, M. J., Mondul, A., Shui, I. M., Theodoratou, E., Nimptsch, K., Lindström, S., Albanes, D., Kühn, T., Key, T. J., Travis, R. C., Vimaleswaran, K. S., Kraft, P., ... Schildkraut, J. M. (2017). Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study. BMJ (Clinical Research Ed.), 359, j4761. https://doi.org/10.1136/bmj.j4761
Dimitrakopoulou VI, et al. Circulating Vitamin D Concentration and Risk of Seven Cancers: Mendelian Randomisation Study. BMJ. 2017 10 31;359:j4761. PubMed PMID: 29089348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study. AU - Dimitrakopoulou,Vasiliki I, AU - Tsilidis,Konstantinos K, AU - Haycock,Philip C, AU - Dimou,Niki L, AU - Al-Dabhani,Kawthar, AU - Martin,Richard M, AU - Lewis,Sarah J, AU - Gunter,Marc J, AU - Mondul,Alison, AU - Shui,Irene M, AU - Theodoratou,Evropi, AU - Nimptsch,Katharina, AU - Lindström,Sara, AU - Albanes,Demetrius, AU - Kühn,Tilman, AU - Key,Timothy J, AU - Travis,Ruth C, AU - Vimaleswaran,Karani Santhanakrishnan, AU - ,, AU - ,, AU - ,, AU - Kraft,Peter, AU - Pierce,Brandon L, AU - Schildkraut,Joellen M, Y1 - 2017/10/31/ PY - 2017/11/2/entrez PY - 2017/11/2/pubmed PY - 2017/11/8/medline SP - j4761 EP - j4761 JF - BMJ (Clinical research ed.) JO - BMJ VL - 359 N2 - 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. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/29089348/Circulating_vitamin_D_concentration_and_risk_of_seven_cancers:_Mendelian_randomisation_study_ L2 - https://www.bmj.com/lookup/pmidlookup?view=long&pmid=29089348 DB - PRIME DP - Unbound Medicine ER -