Genetic Predictors of Circulating 25-Hydroxyvitamin D and Risk of Colorectal Cancer
A partir des données de 13 études portant sur 10 061 cas et 12 768 témoins, cette étude analyse les relations entre six polymorphismes de gènes associés aux niveaux de vitamine D circulante et le risque de cancer colorectal
Background: Experimental evidence has demonstrated an anti-neoplastic role for vitamin D in the colon and higher circulating 25-hydroxyvitamin D (25[OH]D) levels are consistently associated with a lower risk of colorectal cancer (CRC). Genome-wide association studies have identified loci associated with levels of circulating 25(OH)D. The identified SNPs from four gene regions, collectively explain approximately 5% of the variance in circulating 25(OH)D. Methods: We investigated whether six polymorphisms in GC, CYP2R1, CYP24A1 and DHCR7/NADSYN1, genes previously shown to be associated with circulating 25(OH)D levels, were associated with CRC risk in 10,061 cases and 12,768 controls drawn from 13 studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR). We performed a meta-analysis of crude and multivariate-adjusted logistic regression models to calculate odds ratios and associated confidence intervals for SNPs individually, SNPs simultaneously, and for a vitamin D additive genetic risk score (GRS). Results: We did not observe a statistically significant association between the 25(OH)D associated SNPs and CRC marginally, conditionally, or as a GRS, or for colon or rectal cancer separately or combined. Conclusions: Our findings do not support an association between SNPs associated with circulating 25(OH)D and risk of CRC. Additional work is warranted to investigate the complex relationship between 25(OH)D and CRC risk. Impact: There was no association observed between genetic markers of circulating 25(OH)D and CRC. These genetic markers account for a small proportion of the variance in 25(OH)D.