Abstract 4821: Association of polymorphisms in TP53, CXCL2, MDM2, MDM4 and BCL2 genes and proliferative prostate diseases among Lebanese men

Abstract

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 <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<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<0.01), and BPH compared to the controls (OR = 0.17, 95% CI = 0.10-0.28, RR = 0.50, p<0.01); and the ratio of (GG+GD)/DD is higher for subjects with PCa compared to the control (RR = 1.86, p<0.01) and subjects with BPH compared to the controls (RR = 1.85, p<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