Statistical Genetics Group, Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD, 4006, Australia.
Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Rd, Melbourne, VIC, 3004, Australia.
Nat Commun. 2021 Jan 11;12(1):246. doi: 10.1038/s41467-020-20368-w.
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.
先前的 25-羟维生素 D（25（OH）D）与癌症的孟德尔随机化（MR）研究通常采用少数几种变体，并未发现 25（OH）D 与癌症之间存在关系；然而，水平多效性问题无法得到可靠解决。我们使用与 25（OH）D 相关的更大一组变体（从之前的 6 个增加到 74 个 SNP），进行统一的 MR 分析，以重新评估 25（OH）D 与十种癌症之间的关系。我们的研究结果与之前的 MR 研究基本一致，表明除了卵巢癌（OR 0.89；95%CI：每 25（OH）D 浓度变化 1SD，0.82 至 0.96）和基底细胞癌（OR 1.16；95%CI：1.04 至 1.28）外，两者之间没有关系。然而，在多变量 MR 框架中调整了与色素沉着相关的变量后，BCC 的发现结果减弱。在这里，我们报告说，较低的 25（OH）D 不太可能是大多数癌症的因果风险因素，我们的研究提供了比以前更精确的置信区间。
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