Association of rs1042522 Polymorphism with Increased Risk of Prostate Adenocarcinoma in the Pakistani Population and its HuGE Review

Abstract

Prostate adenocarcinoma is one of the leading causes of cancer related mortality in men but still limitedknowledge is available about its associated functional SNPs including rs1042522 (Pro72Arg). The present studywas undertaken to explore the association of this SNP with susceptibility to prostate adenocarcinoma along withits structural and functional impacts in the Pakistani population in a case-control study. Three-dimensionalstructure of human TP53 with Pro72Arg polymorphism was predicted through homology modeling, refined andvalidated for detailed structure-based assessment. We also carried out a HuGE review of the previous availabledata for this polymorphism. Different genetic models were used to evaluate the genotypes association with theincreased risk of PCa (Allelic contrast: OR=0.0.34, 95%CI 0.24-0.50, p=0.000; GG vs CC: OR=0.17, 95%CI0.08-0.38, p=0.000; Homozygous: OR=0.08, 95%CI 0.04-0.15, p=0.000; GC vs CC: OR=2.14, 95%CI 1.01-4.51,p=0.046; Recessive model: OR=0.10, 95%CI 0.05-0.18, p=0.000; Log Additive: OR=3.54, 95%CI 2.13-5.89,p=0.000) except the Dominant model (OR=0.77, 95%CI 0.39-1.52, p=0.46). Structure and functional analysisrevealed that the SNP in the proline rich domain is responsible for interaction with HRMT1L2 and WWOX.In conclusion, it was observed that the Arg coding G allele is highly associated with increased risk of prostateadenocarcinoma in the Pakistani population (p=0.000).