Abstract 1278: Effect modifications of vitamin D receptor common polymorphisms association with prostate cancer by serum vitamin D related behavioral and biological factors

Abstract Background: Several roles have been proposed for vitamin D and the vitamin D receptor (VDR) in prostate cancer (PCa) pathogenesis and progression. However, previous genetic epidemiologic studies have provided limited support linking VDR polymorphisms to PCa due to complexity of vitamin D metabolism and potential gene and environmental interactions. In this study, we investigated the association of VDR genotypes with PCa incidence and aggressiveness in African Americans (AAs) and European Americans (EAs) and if the associations were modified by behavioral and biological factors that influence serum vitamin D levels. Methods: The total of 810 AAs and 487 EAs from Chicago, IL and Washington, D.C. were included in this study. Seven single-nucleotide polymorphisms (SNPs) in and around the VDR gene and 105 ancestry informative markers were genotyped. We performed logistic regression analyses adjusting for relevant variables. Results: In EAs, TaqI (rs73136) and BsmI (rs1544410) minor alleles revealed a protective effect against PCa, while in AAs, FokI (rs2228570) was associated with overall PCa risk (OR=0.74, 95% C.I.: 0.57-0.96). The heterogeneous associations observed in our study could be due to difference in prevalence of vitamin D deficiency between AAs and EAS and effect modifications by behavioral and biological factors that affect serum vitamin D levels. Therefore, we investigated if behavioral and biological factors that influence serum vitamin D modified the associations between VDR polymorphisms and PCa, and we found evidence suggesting that these behavioral and biological factors modify the effect of VDR on PCa. In AAs, we observed statistically significant interaction between two VDR polymorphisms, FokI and TaqI, and vitamin D intake (PInteraction=0.01 and PInteraction=0.03 respectively). We also observed evidence of interactions between VDR gene variants and other behavioral and biological factors that lower serum vitamin D levels in both AAs and EAs. In AAs, calcium intake and skin pigmentation may modify the effects of VDR on PCa. In EAs, BMI may modify the effect of VDR. Conclusions: Although a larger sample size is necessary to confirm the observation, we demonstrated that vitamin D related behavioral and biological factors modify the effect of VDR genotypes on PCa. Impact: The VDR gene is involved in PCa pathogenesis and progression, and polymorphisms in VDR gene and vitamin D are likely to alter the function of the gene. Citation Format: Ken Batai, Adam B. Murphy, Ebony Shah, Chiledum Ahaghotu, Rick A. Kittles. Effect modifications of vitamin D receptor common polymorphisms association with prostate cancer by serum vitamin D related behavioral and biological factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1278. doi:10.1158/1538-7445.AM2017-1278