An Analysis of the Vitamin D Binding Protein Gene Variants and Associated Risks for Prostate Cancer Among African American Men

Epidemiological studies revealed an inversely proportional relationship between vitamin D levels and cancer incidence. Studies suggest single nucleotide polymorphisms (SNPs) of Vitamin D binding protein (DBP) are correlated with serum vitamin D levels. African-American (AA) men have the lowest levels of vitamin D and the highest rates of prostate cancer (PrCa). Since genetic variation is associated with prostate cancer, we hypothesized that DNA variation in DBP is associated with increased risk of PrCa. All reported SNPs within DBP were identified and validated, using HapMap database. We screened for SNPs with a functional consequence on DBP using F-SNP software. A cohort of 716 AA men from Washington DC area were then genotyped for selected SNPs by TaqMan RTM allelic discrimination assays. Statistical analyses were performed using SNPStats, which uses linear regression models. SNPs rs4588 and rs7041 were predicted to have a functional consequence on DBP. After testing the 5 inheritance models, there was no association detected between rs7041 and Prostate Cancer incidence. Rs7041 showed a marginal association using the dominant inheritance model OR (95%CI) 1.52(0.93-2.48) (p-value = 0.09). There was a marginal association found between the haplotype (A-T) (p-value = 0.079) and PrCa incidence. However, the haplotype (C--G) had a significant association with prostate specific antigen (PSA) among African American men (p-value = 0.046). Rs4588 had an association with high Gleason scores in AA men in the log additive model (p-value 0.057). This is the first study to reveal a significant haplotype association between the functional SNPs (rs4588 and rs7041) of DBP with high Gleason scores and PSA levels in AA men. Accordingly, further research is needed regarding the association of these haplotypes effects on the function DBP protein, which may contribute to the increased risk of PrCa seen in AA.