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

• Published in: Nature communications Vol. 12; no. 1; p. 246
• Main 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 25-Hydroxyvitamin D; 45/43; 631/67/68; 692/4028/67/2324; 692/699/67/2195; Basal cell carcinoma; Calciferol; Cancer; Case-Control Studies; Child; Confidence intervals; Consortia; Genetic Predisposition to Disease; Health risks; Humanities and Social Sciences; Humans; Mendelian Randomization Analysis; multidisciplinary; Multivariate Analysis; Neoplasms - genetics; Ovarian cancer; Pigmentation; Pigmentation - genetics; Pleiotropy; Randomization; Risk analysis; Risk Factors; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Sunburn - genetics; Vitamin D; Vitamin D - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-20368-w

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. Studies of the genetic association between vitamin D and cancer risk have typically been underpowered. Here the authors analyse this using Mendelian Randomisation with more than 70 vitamin D variants obtained from the UK Biobank and large-scale data from various consortia, confirming null associations between vitamin D and most cancers.