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 ? 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. Copyright © 2013 Spandidos Publications Ltd. All rights reserved.