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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.

SUBMITTER: Ong JS

PROVIDER: S-EPMC7801600 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Ong Jue-Sheng JS Dixon-Suen Suzanne C SC Han Xikun X An Jiyuan J Liyanage Upekha U Dusingize Jean-Cluade JC Schumacher Johannes J Gockel Ines I Böhmer Anne A Jankowski Janusz J Palles Claire C O'Mara Tracy T Spurdle Amanda A Law Matthew H MH Iles Mark M MM Pharoah Paul P Berchuck Andrew A Zheng Wei W Thrift Aaron P AP Olsen Catherine C Neale Rachel E RE Gharahkhani Puya P Webb Penelope M PM MacGregor Stuart S

Nature communications 20210111 1

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 s ...[more]

PMID: 33431812

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Project description:Background High plasma prekallikrein was reported to be associated with increased risks of stroke, but the causality for these associations remains unclear. We aimed to investigate the associations of genetically predicted plasma prekallikrein concentrations with all-cause stroke, ischemic stroke, 3 ischemic stroke subtypes, and intracerebral hemorrhage (ICH) using a 2-sample Mendelian randomization approach. Methods and Results Seven independent prekallikrein-related single-nucleotide polymorphisms were identified as genetic instruments for prekallikrein based on a genome-wide association study with 1000 European individuals. The summary statistics for all-cause stroke, ischemic stroke, and ischemic stroke subtypes were obtained from the Multiancestry Genome-wide Association Study of Stroke Consortium with 40 585 cases and 406 111 controls of European ancestry. The summary statistics for ICH were obtained from the ISGC (International Stroke Genetics Consortium) with 1545 ICH cases and 1481 controls of European ancestry. In the main analysis, the inverse-variance weighted method was applied to estimate the associations of plasma prekallikrein concentrations with all-cause stroke, ischemic stroke, ischemic stroke subtypes, and ICH. Genetically predicted high plasma prekallikrein levels were significantly associated with elevated risks of all-cause stroke (odds ratio [OR] per SD increase, 1.04 [95% CI, 1.02-1.06]; P=5.44×10-5), ischemic stroke (OR per SD increase, 1.05 [95% CI, 1.03-1.07]; P=1.42×10-5), cardioembolic stroke (OR per SD increase, 1.08 [95% CI, 1.03-1.12]; P=3.75×10-4), and small vessel stroke (OR per SD increase, 1.11 [95% CI, 1.06-1.17]; P=3.02×10-5). However, no significant associations were observed for genetically predicted prekallikrein concentrations with large artery stroke and ICH. Conclusions This Mendelian randomization study found that genetically predicted high plasma prekallikrein concentrations were associated with increased risks of all-cause stroke, ischemic stroke, cardioembolic stroke, and small vessel stroke, indicating that prekallikrein might have a critical role in the development of stroke.

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

Publications

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

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