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.
| Authors | Ong, Jue-Sheng; Dixon-Suen, Suzanne C; Han, Xikun; An, Jiyuan; , ; , ; Liyanage, Upekha; Dusingize, Jean-Cluade; Schumacher, Johannes; Gockel, Ines; Böhmer, Anne; Jankowski, Janusz; Palles, Claire; O'Mara, Tracy; Spurdle, Amanda; Law, Matthew H; Iles, Mark M; Pharoah, Paul; Berchuck, Andrew; Zheng, Wei; Thrift, Aaron P; Olsen, Catherine; Neale, Rachel E; Gharahkhani, Puya; Webb, Penelope M; MacGregor, Stuart |
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| Journal | Nature Communications |
| Pages | 246 |
| Volume | 12 |
| Date | 1/01/2021 |
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| URL | http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1038/s41467-020-20368-w |