Abstract B39: Effect modifiers of vitamin D receptor common polymorphisms on prostate cancer risk
Authors: Batai Ken , Murphy Adam B. , Shah Ebony , Kittles Rick A. 
Published: May 2016

Background: Studies have long proposed the influence of vitamin D and the vitamin D receptor (VDR) on prostate cancer (PCa) initiation and progression, however few studies support the association of VDR variants with PCa. The VDR is a transcription factor which binds to vitamin D and influences the expression of many genes implicated in Pca. Given the complexity of vitamin D availability, we hypothesized that the associations of VDR single-nucleotide polymorphisms (SNPs) with PCa can be modified by various behavioral and biological factors. In this study, we examined VDR SNPs and PCa risk and aggressiveness in African Americans (AAs) and European Americans (EAs) and determined if the associations were modified by behavioral and biological factors that influence serum vitamin D levels, including vitamin D and calcium intake, tobacco use, body mass index (BMI), skin pigmentation, and ultraviolet radiation exposure.

Methods: The total of 810 AAs and 487 EAs from Chicago, IL and Washington, D.C. were included. Seven 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 (respectively C and A allele) revealed a protective effect against PCa, while BsmI AA genotype showed increased odds of having high grade PCa (Gleason Score ≥4+3) in AAs with OR=2.67 (95% C.I.: 1.01-7.11). We also observed evidence of interactions between VDR SNPs and behavioral and biological factors that modify serum vitamin D levels. The TaqI C allele increased odds of PCa in AAs with behavioral and biological factors that reduce serum vitamin D levels, such as low vitamin D intake, current or past tobacco use, and darker skin pigmentation. Among AA men with vitamin D intake &lt;400 IU/day, the TaqI CT/CC genotype significantly increased odds of PCa (P=0.007, OR=1.79, 95% C.I.: 1.17-2.75), but not AA men with high vitamin intake (≥400 IU/day). The interaction between TaqI genotypes and vitamin D intake was significant (P=0.01). The TaqI CT/CC genotype significantly increased odds of PCa among AA men who have smoked or with darker skin pigmentation (P&lt;0.05), but not among AA men who never smoked or with lighter skin pigmentation. On the other hand, the TaqI C allele reduced odds of PCa among EA men with biological factors that decrease serum vitamin D levels. The TaqI CT/CC genotype significantly reduced odds of PCa among obese (BMI≥30) or darker pigmented men (P&lt;0.05), but not among lean or lighter pigmented men. The interaction between BMI and TaqI genotypes in EA men was significant (P=0.05).

Conclusion: Although a larger sample size is necessary to confirm our observations, our results suggest that the VDR gene is involved in PCa pathogenesis and progression, but the effects of VDR gene on PCa are modified by behavioral and biological factors that modify serum vitamin D levels.

Citation Format: Ken Batai, Adam B. Murphy, Ebony Shah, Rick A. Kittles. Effect modifiers of vitamin D receptor common polymorphisms on prostate cancer risk. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B39.