Background: The vitamin D receptor (VDR) and binding protein (DBP) mediate the cellular transport, activity, and anti-tumor action of 1,25-dihydroxyvitamin D3 [1,25-(OH)(2)D3]. The purpose of this investigation is to determine whether novel single nucleotide polymorphisms (SNPs) within the transcriptional regulatory regions of the VDR and DBP are associated with prostate cancer risk.
Methods: Novel SNPs were identified in the VDR and DBP transcription regulatory gene regions and genotyped in a case-control study using male subjects with (n=258) or without (n=434) prostate cancer.
Results: African-American men who possessed at least one variant VDR-5132 C allele had a increased risk of prostate cancer (OR=1.83; 95% CI: 1.02, 3.31). Further study revealed that the VDR-5132 T/C SNP eliminates a GATA-1 transcription factor-binding site.
Conclusion: The VDR-5132 T/C SNP, resulting in potential elimination of the GATA-1 transcription factor-binding site, may increase prostate cancer susceptibility in African-Americans. Confirmation of these findings is needed in larger observational studies.
(c) 2005 Wiley-Liss, Inc.