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Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study

医学 前列腺癌 肿瘤科 内科学 胰腺癌 乳腺癌 结直肠癌 优势比 癌症 卵巢癌 维生素D与神经学 单核苷酸多态性 肺癌 基因型 生物 遗传学 基因
作者
Vasiliki Dimitrakopoulou,Konstantinos K. Tsilidis,Philip Haycock,Niki Dimou,Kawthar Al-Dabhani,Richard M. Martin,Sarah J. Lewis,Marc J. Gunter,Alison M. Mondul,Irene M. Shui,Evropi Τheodoratou,Katharina Nimptsch,Sara Lindström,Demetrius Albanes,Tilman Kühn,Timothy J. Key,Ruth C. Travis,Karani S. Vimaleswaran,Peter Kraft,Brandon L. Pierce,Joellen M. Schildkraut
出处
期刊:BMJ [BMJ]
卷期号:: j4761-j4761 被引量:153
标识
DOI:10.1136/bmj.j4761
摘要

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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