Abstract 5304: Association of prostate cancer and benign prostate hyperplasia with polymorphisms in VDR gene, CYP17 gene and SRD5A2 gene among Lebanese men.

Specific aim: To investigate the relationship between genetic polymorphisms in vitamin D receptor (VDR) gene, cytochrome P-450 steroid 17α-hydroxylase/17, 20 lyase gene (CYP17 gene) and steroid 5α reductase type II gene (SRD5A2 gene) and prostate cancer (PC) and benign prostate hyperplasia (BPH) among Lebanese men. Methods: DNA extracted from blood of 47 subjects with clinical PC, 76 subjects with BPH and 81 subjects with no prostrate-related pathologies (all subjects 50-70 years in age) was tested for single nucleotide polymorphisms in VDR and CYP17 genes and variable numbers of TA repeats in the SRD5A2 gene (0 or 9 repeats) using polymerase chain reaction followed by restriction fragment-length polymorphism analysis and/or electrophoretic separation. Association between PC and/or BPH and the genotypes was assessed by calculating the odds ratio (OR) and 95% confidence intervals (CI). The relative risk (RR) of PC and/or and BPH associated with the recessive alleles was estimated using the equation RR= (a/(a+b))/(c/(c+d)), where a is the number of subjects with PC or BPH who are homozygous recessive, b is the number of subjects with PC or BPH who are homozygous dominant or heterozygous, c is the number of control subjects who are homozygous recessive and d is the number of control subjects who are homozygous dominant or heterozygous in a particular gene. Results: The genotype ff (for Fok I C to T), bb (for Bsm I A to G), aa (for Apa I G to T) and tt (for Taq I T to C) of VRD gene are not associated with elevated risk for PC or BPH (for ff; OR: 0.5231- 0.5818, 95% CI: 0.0390-1.1098, RR: 0.7116-0.7579, 95% CI: 0.4586- 1.0807; for bb; OR: 0.1476-0.3850, 95% CI: 0.0603-0.9081, RR: 0.3068-0.5137, 95% CI: 0.1462-0.9719; for aa; OR: 0.3193-0.5478, 95% CI: 0.2203-1.1580, RR: 0.6256-0.7371, 95% CI: 0.6256-0.7371, 95% CI: 0.4375-1.0999; for tt: OR: 0.7197-1.1142; 95% CI: 0.3066-2.6989, RR: 0.7849-1.2434, 95% CI: 0.4146-1.9431). The genotype A2/A2 for CYP17 gene was only marginally associated with elevated risk for PC or BPA (OR: 0.7761-1.0860, 95% CI: 0.2751-2.4471, RR: 0.8073-1.0658, 95% CI: 0.3342-2.0858). Although not statistically significant at 0.05 level of significance, genotype (TA)9/(TA)9 showed an association with PC and BPH (OR:1.7325-1.9268, 95% CI: 0.2618-14.1801; RR: 1.7017-1.8837, 95% CI: 0.2748-12.91). Conclusions: The data indicates that among Lebanese men, the Fok I, Bsm I, Apa I and Taq I polymorphisms in VDR gene are not associated with elevated risks of developing PC or BPH, alyhough A2/A2 allele of CYP17 gene can be marginally associated and (TA)9/(TA)9 allele of SRD5A2 gene may be substantially associated with PC and BPH but the finding needs to be confirmed in further studies. Citation Format: Ruhul H. Kuddus, Asmahan A. El Ezzi, Mohammed A. El-Saidi. Association of prostate cancer and benign prostate hyperplasia with polymorphisms in VDR gene, CYP17 gene and SRD5A2 gene among Lebanese men. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5304. doi:10.1158/1538-7445.AM2013-5304