Role of Functional Polymorphisms of P53 and P73 Genes with the Risk of Prostate Cancer in a Case-Control Study from Northern India

Abstract

P53 gene variants BstUI RFLP at codon 72 in exon 4, 16-bp tandem repeat in intron 3 and Msp I RFLP in intron 6 and P73 gene variants of G4C14-to-A4T14 (GC/AT), exon 2 polymorphism, which respectively codes for four functionally different protein isoforms, have been shown to modulate susceptibility to different types of human neoplasms. We undertook this study to evaluate the role of P53 and P73 SNPs in prostate cancer in a Northern Indian population. P53 and P73 genotypes were assessed in a hospital-based case-control study comprised of 177 prostate cancer cases and 265 healthy controls. After the extraction of genomic DNA from blood, genotyping was done using PCR-RFLP and PCR-CTPP methods, respectively. A significant association was found in P53 intron 6 G>A and P53 R72P G>C polymorphism with PCa risk. In P53 intron 6 G>A polymorphism the heterozygous genotype (GA) showed marginal risk with the disease (OR = 1.48, 95% CI = 0.999-2.220). Individuals with heterozygous genotype only (GC) of P53 R72P G>C polymorphism demonstrated PCa risk (OR = 1.5, 95% CI = 1-2.199). Haplotypes G-C-D and A-G-D (OR = 1.58, 95% CI = 1.125-2.241 and OR = 2.70, 95% CI = 1.767-4.143, respectively) were also found to be associated with an increased risk of PCa. Our study provided evidence that the P53 intron 6 G>A and R72P G>C polymorphisms were associated with a higher risk of prostate cancer in a Northern Indian population.