Genetic variability of DNA repair mechanisms influences treatment outcome of gastric cancer

Abstract

The aim of the current study was to investigate the role of polymorphisms in DNA repair pathways on the clinical outcome of gastric cancer patients treated with platinum-based chemotherapy. A total of 380 gastric cancer patients treated with platinum-based chemotherapy were included in the present study. The genotypes of ERCC1 rs11615 (Asn118Asn) and rs3212986 (*197G>T), ERCC2 rs1799793 (Asn312Asp) and rs13181 (Lys751Gln), NBN rs1805794 (Gln185Gln) and rs1063054 (*1209A>C), RAD51 rs1801321 (−61G>T) and rs12593359 (*502T>G), and XRCC3 rs861539 (Thr241Met) were determined by polymerase chain reaction-restriction fragment length polymorphism, according to the manufacturer's instructions. The TC+CC genotypes of ERCC1 rs11615 and GA+AA genotypes of ERCC2 rs1799793 were found to be associated with improved response to chemotherapy, with an adjusted odds ratio of 1.66 (95% CI, 1.07–2.56) and 1.61 (95% CI, 1.05–2.49), respectively. Based on the results of Cox analysis, patients with TC+CC genotypes of ERCC1 rs11615 and GA+AA genotypes of ERCC2 rs1799793 exhibited a significantly decreased risk of mortality, with hazard ratios of 1.71 (95% CI, 1.06–2.72) and 1.97 (95% CI, 1.28–3.03), respectively. In conclusion, these results suggest that ERCC1 rs11615 and ERCC2 rs1799793 in the DNA repair pathways may be used as predictive factors of the clinical outcome in gastric cancer patients.