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

Jue-Sheng Ong (), Suzanne C. Dixon-Suen, Xikun Han, Jiyuan An, Upekha Liyanage, Jean-Cluade Dusingize, Johannes Schumacher, Ines Gockel, Anne Böhmer, Janusz Jankowski, Claire Palles, Tracy O’Mara, Amanda Spurdle, Matthew H. Law, Mark M. Iles, Paul Pharoah, Andrew Berchuck, Wei Zheng, Aaron P. Thrift, Catherine Olsen, Rachel E. Neale, Puya Gharahkhani, Penelope M. Webb and Stuart MacGregor
Additional contact information
Jue-Sheng Ong: QIMR Berghofer Medical Research Institute
Suzanne C. Dixon-Suen: Cancer Council Victoria
Xikun Han: QIMR Berghofer Medical Research Institute
Jiyuan An: Queensland University of Technology, QLD
Upekha Liyanage: QIMR Berghofer Medical Research Institute
Jean-Cluade Dusingize: QIMR Berghofer Medical Research Institute
Johannes Schumacher: Philipps University of Marburg
Ines Gockel: University Hospital Leipzig
Anne Böhmer: University of Bonn, School of Medicine & University Hospital Bonn
Janusz Jankowski: University of Arab Emirates University
Claire Palles: University of Birmingham
Tracy O’Mara: QIMR Berghofer Medical Research Institute
Amanda Spurdle: QIMR Berghofer Medical Research Institute
Matthew H. Law: QIMR Berghofer Medical Research Institute
Mark M. Iles: University of Leeds
Paul Pharoah: University of Cambridge
Andrew Berchuck: Division of Gynecologic Oncology, Duke University Medical Center
Wei Zheng: Vanderbilt University School of Medicine
Aaron P. Thrift: Baylor College of Medicine
Catherine Olsen: University of Queensland
Rachel E. Neale: QIMR Berghofer Medical Research Institute
Puya Gharahkhani: QIMR Berghofer Medical Research Institute
Penelope M. Webb: QIMR Berghofer Medical Research Institute
Stuart MacGregor: QIMR Berghofer Medical Research Institute

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20368-w

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