Abstract 1653: Genetic variation in the vitamin D pathway and risk for colorectal cancer in African Americans

Abstract

Abstract Background: Colorectal cancer (CRC) is the third leading cause of cancer-related death in both sexes in the United States. There is a large disparity in both CRC incidence and survival between African Americans (AAs) and all other US racial groups. Differences in serum vitamin D levels could contribute to this disparity because vitamin D is thought to protect against CRC and AAs have lower serum vitamin D levels. In addition, genetic variants in vitamin D-related genes could modify the association between vitamin D levels and CRC risk. Methods: We tested for associations between CRC and 39 single nucleotide polymorphisms (SNPs) in vitamin D-related genes (CYP27A1, GC, CYP3A4, CYP2R1, DHCR7/NADSYN1, VDR, CYP27B1 and CYP24A1). We genotyped 357 AAs cases and 443 AA controls from the North Carolina Colorectal Cancer Study. We calculated odds ratios (OR) using logistic regression, assuming an additive genetic model and controlling for age, gender, and ancestry. We also analyzed SNP associations for colon and rectal cancer cases separately. We analyzed linkage disequilibrium and haplotype association using Haploview. Results: Associations (p<0.05) were detected between CRC and two SNPs in the vitamin D binding protein gene GC, rs3755967 (OR, 0.69; P = .039,) and rs16847024 (OR, 1.50; P = .047,). We also detected an association with a SNP in the 24-hydroxylase gene CYP24A1, rs73913755 (OR, 0.75; P = .034,), which degrades vitamin D. A trend for association was detected in the 25-hydroxylase gene CYP2R1, rs10741657 (OR, 0.79; P = .051), which converts cholecalciferol into calcidiol. When we analyzed colon and rectal cancers separately, only one SNP was associated with colon cancer whereas 9 SNPs were associated with rectal cancer. In particular, rs73913755 (OR, 0.39; P = 3 x 10-7) was statistically significant even after adjustment for multiple testing. Conclusion: We tested vitamin D-related SNPs and found suggestive evidence that they influence the risk of developing CRC in AAs, with differences in risk between the colon and rectum. Comparison of these data with data from US whites could shed light on disparities in these different US populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1653. doi:1538-7445.AM2012-1653