Abstract 6130: Association of vitamin D-related genetic variants and prostate cancer risk in Black men

Abstract

Abstract Background: What we know of the relationship between vitamin D status and prostate cancer has largely been characterized among men of European ancestry, hereafter referred to as “White”. Research among White men indicate positive associations between circulating vitamin D status, as measured by concentrations of 25-hydroxyvitamin D (25(OH)D), with prostate cancer risk, and that genetic scores based on genome-wide associated single nucleotide polymorphisms (SNPs) reflecting high vs. low 25(OHD) is positively associated with aggressive disease. Limited research exists elucidating this relationship among men of African ancestry, hereafter referred to as “Black”. This is despite the fact that Black populations experience chronically lower circulating 25(OH)D, and ancestry-specific differences in genetic variants in some vitamin D-related genes. Given the paucity of research in this area, we examined the role of genetic variants in six commonly studied genes in the vitamin D pathway involved in synthesis (CYP27A1 and CYP27B1), transport (GC), activity (VDR and RXR), and metabolism (CYP24A1) in relation to prostate cancer among Black men. Methods: We assessed a total of 78 candidate SNPs in six vitamin D pathway genes that were either previously associated with circulating 25(OHD) and/or associated with prostate cancer risk in studies of White men. We compared vitamin D gene SNP associations with prostate cancer in Black and White men using summary statistics from a large GWAS of over 10,000 prostate cancer cases and 10,000 controls among Black men and over 85,000 cases and 91,000 controls among White men. A statistical significance threshold of 0.00064 (0.05/78 candidate SNPs) was used to adjust for multiple comparisons. Results: None of the examined SNPs were significantly associated with prostate cancer risk among Black men after adjustment for multiple comparisons. However, four SNPs were nominally significant in Black men, including two in RXR [rs41400444 OR=1.09, 95% CI: 1.01-1.17, P = 0.024 and rs10881574 OR = 0.93, 0.867-0.999, P = 0.04556] and two in VDR [rs2853563 OR = 1.07, 1.012-1.13, P = 0.0173 and rs1156882 OR = 1.06, 1.00-1.12, P = 0.0495]. The latter SNP rs1156882 was also positively associated with prostate cancer risk in White men (OR = 1.035, 1.02-1.06, P = 0.00024), along with VDR SNP rs4516035 (OR = 1.027, 1.012-1.042, P = 0.00055), both after correction for multiple comparisons. Conclusions: We observed non-significant, though suggestive, associations between genetic variants in vitamin D pathway genes previously associated with prostate cancer or vitamin D levels in White populations and prostate cancer risk in Black men. Future research exploring the potential role of vitamin D pathway genes and prostate cancer in Black men – a population at high risk both for low circulating vitamin D and prostate cancer - will need to identify vitamin D-related genetic variants specific to carcinogenesis in Black men. Citation Format: Tracy M. Layne, Joseph H. Rothstein, Xiaoyu Song, Weiva Sieh, Robert J. Klein. Association of vitamin D-related genetic variants and prostate cancer risk in Black men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6130.