Association of PARK-2 Non-synonyms Polymorphisms and Their In Silico Validation Among North Indian Colorectal Cancer Patients.

Abstract

PARK2 is a potential tumour suppressor gene and its genetic alterations (regionic loss) are common across many human cancers. The association of PARK2 germline variations (SNPs) with Parkinson's has been shown, but their association in development and progression of cancer remains elusive. The aim of this study was to identify association of PARK2 polymorphisms (rs1801474, rs1801334) with colorectal cancer in a case control study design. This case control study included a total of 650 genetically unrelated subjects comprising 300 colorectal cancer cases and 350 healthy controls belonging to North Indian. Both SNPs were analyzed using the PCR-RFLP assay. Statistical analysis for describing risk and association was performed using SPSS-17 software. Structural deviations due to non- synonymous substitutions (S167N and D394N) were analyzed using MD simulations. The genotype distributions of both the SNPs were in Hardy-Weinberg equilibrium. For both the polymorphisms, the allelic model showed statistically significant risk with OR ~ 1.3. Many of the associations remained significant even after Bonferroni correction (P < 0.00125). The result suggested that both S167N and D394N were deviated from wild type and structures and were stable after 5ns. The average value of RMSD for backbone atoms was calculated from 5 to 10ns molecular dynamics simulation data. In conclusion, our study revealed a significant association of PARK2 SNPs with colorectal cancer as well as their relations with other clinical parameters highlighting their contribution towards colorectal cancer susceptibility in North Indian population.