Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study. (28th December 2018)

• Record Type: Journal Article
• Authors: Jiang, Xia; Dimou, Niki L; Al-Dabhani, Kawthar; Lewis, Sarah J; Martin, Richard M; Haycock, Philip C; Gunter, Marc J; Key, Timothy J; Eeles, Rosalind A; Muir, Kenneth; Neal, David; Giles, Graham G; Giovannucci, Edward L; Stampfer, Meir; Pierce, Brandon L; Schildkraut, Joellen M; Warren Andersen, Shaneda; Thompson, Deborah; Zheng, Wei; Kraft, Peter; Tsilidis, Konstantinos K
• Is Part Of: International journal of epidemiology. Volume 48:Number 5(2019)
• Page Start: 1416
• Page End: 1424
• Publication Date: 2018-12-28
• Subjects: serum vitamin D concentrations -- malignancy -- breast -- prostate -- Mendelian randomization; Epidemiology -- Periodicals; 614.4
• DOI: 10.1093/ije/dyy284
• Languages: English
• ISSNs: 0300-5771

Abstract

Abstract: Background: Observational studies have suggested an association between circulating vitamin D concentrations [25(OH)D] and risk of breast and prostate cancer, which was not supported by a recent Mendelian randomization (MR) analysis comprising 15 748 breast and 22 898 prostate-cancer cases. Demonstrating causality has proven challenging and one common limitation of MR studies is insufficient power. Methods: We aimed to determine whether circulating concentrations of vitamin D are causally associated with the risk of breast and prostate cancer, by using summary-level data from the largest ever genome-wide association studies conducted on vitamin D ( N = 73 699), breast cancer ( N case = 122 977) and prostate cancer ( N case = 79 148). We constructed a stronger instrument using six common genetic variants (compared with the previous four variants) and applied several two-sample MR methods. Results: We found no evidence to support a causal association between 25(OH)D and risk of breast cancer [OR per 25 nmol/L increase, 1.02 (95% confidence interval: 0.97–1.08), P = 0.47], oestrogen receptor (ER)+ [1.00 (0.94–1.07), P = 0.99] or ER− [1.02 (0.90–1.16), P = 0.75] subsets, prostate cancer [1.00 (0.93–1.07), P = 0.99] or the advanced subtype [1.02 (0.90–1.16), P = 0.72] using the inverse-variance-weighted method. Sensitivity analyses did not reveal any sign of directional pleiotropy. Conclusions: Despite its almost five-fold augmented sample size and substantially improved statistical power, our MR analysis does not support a causal effect of circulating 25(OH)D concentrations on breast- or prostate-cancer risk. However, we can still not exclude a modest or non-linear effect of vitamin D. Future studies may be designed to understand the effect of vitamin D in subpopulations with a profound deficiency.