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

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posted on 2021-01-01, 00:00 authored by J S Ong, Suzanne Dixon-SuenSuzanne Dixon-Suen, X Han, J An, R Fitzgerald, M Buas, M D Gammon, D A Corley, N J Shaheen, L J Hardie, N C Bird, B J Reid, W H Chow, H A Risch, W Ye, G Liu, Y Romero, L Bernstein, A H Wu, D E Whiteman, T Vaughan, M Agee, B Alipanahi, A Auton, R K Bell, K Bryc, S L Elson, P Fontanillas, N A Furlotte, D A Hinds, K E Huber, A Kleinman, N K Litterman, M H McIntyre, J L Mountain, E S Noblin, C A M Northover, S J Pitts, J F Sathirapongsasuti, O V Sazonova, J F Shelton, S Shringarpure, C Tian, J Y Tung, V Vacic, C H Wilson, U Liyanage, J C Dusingize, J Schumacher, I Gockel, A Böhmer, J Jankowski, C Palles, T O’Mara, A Spurdle, M H Law, M M Iles, P Pharoah, A Berchuck, W Zheng, A P Thrift, C Olsen, R E Neale, P Gharahkhani, P M Webb, S MacGregor
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

History

Journal

Nature Communications

Volume

12

Article number

246

Pagination

1 - 10

Publisher

Nature Publishing

Location

London, Eng.

ISSN

2041-1723

eISSN

2041-1723

Language

eng

Publication classification

C1 Refereed article in a scholarly journal