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.

Metadata

Item Type:	Article
Authors/Creators:	Ong, J-S Dixon-Suen, SC Han, X An, J Liyanage, U Dusingize, J-C Schumacher, J Gockel, I Böhmer, A Jankowski, J Palles, C O’Mara, T Spurdle, A Law, MH Iles, MM https://orcid.org/0000-0002-2603-6509 Pharoah, P Berchuck, A Zheng, W Thrift, AP Olsen, C Neale, RE Gharahkhani, P Webb, PM MacGregor, S
Copyright, Publisher and Additional Information:	© The Author(s) 2021. s This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
Dates:	Accepted: 26 November 2020 Published (online): 11 January 2021 Published: December 2021
Institution:	The University of Leeds
Academic Units:	The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Clinical & Population Science Dept (Leeds)
Funding Information:	Funder Grant number National Cancer Institute 0000686290
Depositing User:	Symplectic Publications
Date Deposited:	20 Jan 2021 16:05
Last Modified:	20 Jan 2021 16:05
Status:	Published
Publisher:	Nature Research
Identification Number:	10.1038/s41467-020-20368-w
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:170223

Download

Published Version

Filename: s41467-020-20368-w.pdf

Licence: CC-BY 4.0

CLICK TO DOWNLOAD

CORE (COnnecting REpositories)

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

Abstract

Metadata

Download

Published Version

Export

Statistics