A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization

Abstract

Previous Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.

之前有关维生素D和癌症的孟德尔随机化研究使用的工具变量SNP很少，它们的研究都发现维生素D和癌症没有关系。然而水平多效性的问题一直没有得到可靠的解决，本文使用更多的与维生素D相关的SNP（74个SNP，之前是6个），借助孟德尔随机化的方法来探究维生素D和始终癌症之间的因果关系，研究最终发现维生素D和大多数的癌症发病没有关系，本研究提供了比以前更精确的置信区间。

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