Exploring causality in the association between circulating 25-hydroxyvitamin D and colorectal cancer risk: a large Mendelian randomisation study

Abstract

2018 * Received: 17 April 2018 * Accepted: 6 July 2018 * Published: 14 August 2018 Open Peer Review reports Abstract Background Whilst observational studies establish that lower plasma 25-hydroxyvitamin D (25-OHD) levels are associated with higher risk of colorectal cancer (CRC), establishing causality has proven challenging. Since vitamin D is modifiable, these observations have substantial clinical and public health implications. [...]we examined the association between our instrumental GRS of 25-OHD and common confounders including age, sex, BMI, physical activity, assessment centre, smoking status and alcohol consumption based on available data in SOCCS (n = 9746) and UK biobank (n = 11,382) controls to test the potential violation of the second MR assumption. [...]none of the genetic variants used in our analysis were cited by the NHGRI-EBI Catalogue of published GWAS as associated with known CRC risk confounders (such as height, BMI, alcohol consumption, smoking, type II diabetes, inflammatory bowel disease, adenomas) [55]. [...]due to the low proportion of 25-OHD variance (2.84%) explained by the genetic variants and relatively small sample size, our individual level data analysis did not reach the desired power (< 0.80) assuming true causal effects of 25OHD on CRC risk was similar to the effect observed in the observational SOCCS case–control study (OR 0.83).