Background: The aim of the study was to investigate any associations between benign prostate hyperplasia (BPH) and single nucleotide polymorphisms (SNPs) in the VDR gene (FokI, BsmI, ApaI and TaqαI loci) and the CYP17 gene (MspA1I locus), as well as TA repeat polymorphism in SRD5A2 gene among Lebanese men. Materials and Methods: DNA extracted from blood of 68 subjects with confirmed BPH and 79 age-matched controls was subjected to PCR/PCR-restriction fragment length polymorphism analysis. The odds ra=tio (OR) of having a genotype and the relative risk (RR) of developing BPH for having the genotype were calculated and the alleles were designated risk-bearing or protective. Results: Our data indicated that the A and B alleles of the VDR ApaI and BsmI SNPs were highly associated with increased risk of BPH (p=0.0168 and 0.0002, respectively). Moreover, 63% of the controls compared to 43% of the subjects with BPH were homozygous for none of the risk-bearing alleles (p=0.0123) whereas 60% of the controls and 28% of the subjects with BPH were homozygous for two or more protective alleles (p<0.0001). Conclusions: For the first time, our study demonstrated that ApaI and BsmI of the VDR gene are associated with risk of BPH among Lebanese men. Our study also indicated that overall polymorphism profile of all the genes involved in prostate physiology could be a better predictor of BPH risk.

Background. Angiotensin I converting enzyme (ACE) insertion (I) and 287 bp Alu repeat DNA fragment deletion (D) polymorphisms have been indicated in various cancers. Here, we investigated I/D polymorphisms in prostate cancer (PCa) and benign prostate hyperplasia (BPH) among Lebanese men. Methods. Blood DNA extracted from 69 control subjects, 69 subjects with clinically confirmed PCa, and 69 subjects with clinical BPH, all the subjects were aged 50 years or older, was subjected to the polymerase chain reaction. The PCR products were resolved in polyacrylamide gels to determine II, ID, and DD genotypes. The odds ratios (OR), 95% confidence intervals (CI), and p values of the allele frequencies and genotype ratios were calculated for establishing possible association of the alleles and/or genotypes and PCa and/or BPH. Results. The proportions of II, ID, and DD genotypes were significantly different from Hardy–Weinberg equilibrium for BPH and PCa groups (but not the control group), mostly due to overabundance of the ID genotypes. There was no significant difference in the I and D allele frequencies between the control groups and the affected groups. The ratio of (DD + ID)/II is significantly lower among the control group compared to the BPH group (RR = 8.92, p=0.042), and the ratio of ID/(DD + II) is significantly lower among the control group compared to the affected groups (RR = 1.99, p=0.021). Conclusions. Our data indicate that the D allele of the I/D polymorphisms of the ACE gene is associated with increased risk of BPH, and the ID genotype is a risk factor for both BPH and PCa among Lebanese males.

Specific Aims: To investigate possible relationships between certain polymorphisms in p53 protein (TP53) gene, chemokine (C-X-C motif) ligand 2 (CXCL-2) gene, mouse double minute 2 homologue (MDM2) gene, MDM4 protein (MDM4) gene and B cell lymphoma 2 protein (BCL2) gene and benign prostate hyperplasia (BPH) and prostate cancer (PCa) among middle-aged Lebanese men. Methods: Blood was collected from volunteer prostate disease screening campaign participants ages 50-70. DNA was extracted from peripheral blood leucocytes of 85 donors diagnosed with clinical PCa, 178 donors diagnosed with BPH, and 140 donors with no prostrate-related pathologies. The 72 Arg/pro polymorphism of TP53 gene, 801 G/A polymorphism of CXCL2 gene, 309 G/T polymorphism of MDM2 gene, 103 T/C and D153G polymorphisms of MDM4 gene and 938 C/A polymorphism of BCL2 genes was investigated by polymerase chain reaction/restriction fragment-length polymorphism analysis. The genotype of the subjects for each of the genes was determined and allelic frequency was calculated. Association between the genotypes and PCa and BPH was estimated by calculating the odds ratio (OR) and 95% confidence intervals (CI). The relative risk (RR) of PCa or BPH for having a particular genotype was also calculated using MedCalc statistical software. The null hypotheses were rejected with a p value of &lt;0.05%. Results: There is no association between the examined polymorphisms of the TP53 gene, CXCL2 gene, MDM2 gene and BCL2 gene and BPH or PCa. The ratio of C/T alleles for the 103 T/C locus and the ratio of D/G alleles for D153G locus of MDM4 are lower for subjects with PCa and BPH compared to the controls (p&lt;0.01 for both loci). The ratio of (CC+CT)/TT is lower for subjects with PCa compared to the control (OR = 0.12, 95% CI = 0.06-0.22, RR = 0.39, p&lt;0.01), and BPH compared to the controls (OR = 0.17, 95% CI = 0.10-0.28, RR = 0.50, p&lt;0.01); and the ratio of (GG+GD)/DD is higher for subjects with PCa compared to the control (RR = 1.86, p&lt;0.01) and subjects with BPH compared to the controls (RR = 1.85, p&lt;0.01). Conclusions: There is no statistically significant association between polymorphisms in TP53 gene, CXCL2 gene, MDM2 gene and BCL2 gene and PCa or BPH but the C allele of 103 T/C locus and the G allele of the D153G locus of MDM4 are risk factors for both PCa and BPH among Lebanese men. Citation Format: Ruhul H. Kuddus, Asmahan A. El Ezzi, Mohammed A. El-Saidi, Scott Baker, Wissam Zaidan. Association of polymorphisms in TP53, CXCL2, MDM2, MDM4 and BCL2 genes and proliferative prostate diseases among Lebanese men. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4821. doi:10.1158/1538-7445.AM2015-4821