Impact of ERCC2 Lys751Gln (rs13181), ERCC2 Asp312Asn (rs1799793) and XRCC1 Arg399Gln (rs25487) polymorphisms on the risk of prostate cancer among cases from the central region of Saudi Arabia

Abstract

This study was undertaken to investigate an association between genetic variants of ERCC2 (Lys751Gln), ERCC2 (Asp312Asn) or XRCC1 (Arg399Gln) polymorphisms with the risk of prostate cancer (PC) in Saudi population. This is a case-control study conducted on 124 PC patients and 425 healthy human controls. Blood samples were used for DNA extraction and gene polymorphisms for ERCC2 (Lys751Gln), ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln). The risk of the associations was calculated by odds ratio (OR) and 95% confidence interval (CI). The data demonstrated no significant associations between ERCC2 (Lys751Gln) polymorphism and PC risk, whereas ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) polymorphisms were found to be significantly associated with PC risk (OR of 2.2, 95% CI, 1.1–4.1; p = 0.02) and (OR of 2.4, 95% CI, 1.3–4.5; p = 0.005), respectively. Likewise, recessive genotype models also showed significant association of ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) polymorphisms with PC risk (p = 0.009). Interestingly, these genetic associations were more pronounced in aged populations (p = 0.003) as well as in smokers (p < 0.0001). Combination of ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) genotypes showed strong association with the risk of PC onset (p < 0.001). These novel findings indicate that ERCC2 (Lys751Gln) polymorphism was not associated with risk of PC, whereas ERCC2 (Asp312Asn) and XRCC1 (Arg399Gln) polymorphisms showed strongly associated with the increased risk of PC. Combination of ERCC2 (Asp312Asn) and XRCC1 (Arg399 Gln) genotypes also showed strong association with increased risk of PC. In addition, more risk of PC onset was noticed in aged population and for those who were reported to have smoking history.