Influences of ERCC1, ERCC2, XRCC1, GSTP1, GSTT1, and MTHFR polymorphisms on clinical outcomes in gastric cancer patients treated with EOF chemotherapy.

Abstract

This study investigated the associations between genetic polymorphisms of six genes involved in DNA repair, detoxification pathways, and fluoropyrimidine metabolism and clinical outcomes in MGC patients receiving EOF treatment. This retrospective study included 108 Chinese MGC patients receiving EOF as first-line chemotherapy. Nine single nucleotide polymorphisms (SNPs) of six genes (ERCC1 rs2298881, ERCC2 rs13181 and rs1799793, XRCC1 rs25487 and rs25489, GSTP1 rs1695, GSTT1 rs2266637, and MTHFR rs1801133 and rs1801131) were genotyped, and the associations between each SNP and clinical outcome were analyzed. XRCC1 rs25487 A allele was significantly associated with progression disease (PD) to EOF (p = 0.002), and patients with AA genotype had significantly poorer progression-free survival (PFS) (p = 0.001) and overall survival (OS) (p = 0.041) compared with patients with the G allele (GG + GA). ERCC2 rs13181 G allele was significantly associated with PD (p = 0.026), and G carriers (GG + GT) tended to have poorer PFS (p = 0.092) than TT homozygotes. ERCC2 rs1799793 GA genotype was associated with unfavorable PFS (p = 0.034) and a tendency toward poorer OS (p = 0.090) compared with GG homozygotes. Patients were categorized as either good (0 risk factors) or poor risk (≥1 unfavorable SNPs) using a prognostic index based on XRCC1 rs25487 AA, ERCC2 rs13181 (GG + GT), and ERCC2 rs1799793 GA genotypes, with median OS and PFS of 534days, 281days (p = 0.009) and 206days, and 123days (p < 0.001), respectively. These results suggest that the prognostic index comprising XRCC1 rs25487, ERCC2 rs13181, and rs1799793 polymorphisms may be a useful predictor of clinical outcomes in MGC treated with EOF.