Genetic polymorphisms of ERCC1-118, XRCC1-399 and GSTP1-105 are associated with the clinical outcome of gastric cancer patients receiving oxaliplatin-based adjuvant chemotherapy

Abstract

The aim of the present study was to determine whether specific molecular parameters may serve as predictors of treatment outcomes and toxicity of oxaliplatin (OXA)‑based chemotherapy, which is used as an adjuvant treatment in resected gastric cancer. All gastric cancer patients examined in the study received an OXA/5‑fluorouracil chemotherapeutic regimen. Genetic polymorphisms of certain platinum‑related genes were determined by the TaqMan 5' nuclease assay and direct sequencing. Relapse‑free survival (RFS), overall survival (OS) and toxicity were evaluated according to each genotype. Following adjustment for the most relevant clinical variables, excision repair cross‑complimentary group 1 (ERCC1)‑118 and X-ray repair cross-complementing protein 1 (XRCC1‑399) demonstrated significant predictive value for RFS and OS. We also demonstrated that carrying at least one variant XRCC1 Arg399Gln or glutathione S-transferase π 1 (GSTP1) Ile105Val allele significantly increased the risk of any grade 3 or 4 hematological toxicity. In particular, carrying at least one variant GSTP1 Ile105Val allele was also significantly correlated with an increased risk of grade 3 or 4 gastrointestinal toxicity and neurotoxicity. Our data suggested that gastric cancer patients harboring ERCC1‑118 C/C and XRCC1‑399 A/G or A/A genotypes may benefit from receiving OXA‑based adjuvant chemotherapy, and carrying at least one variant XRCC1 Arg399Gln or GSTP1 Ile105Val allele may contribute to the occurrence of adverse drug effects associated with OXA‑based chemotherapy.