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.
Authors	Yong-Ping Liu, Yang Ling, Qiu-Feng Qi, Ya-Ping Zhang, Chang-Song Zhang, Chang-Tai Zhu, Mei-Hua Wang, Yao-Dong Pan
Journal	Molecular medicine reports (Mol Med Rep) Vol. 7 Issue 6 Pg. 1904-11 (Jun 2013) ISSN: 1791-3004 [Electronic] Greece
PMID	23604281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents DNA-Binding Proteins Organoplatinum Compounds X-ray Repair Cross Complementing Protein 1 XRCC1 protein, human Oxaliplatin GSTP1 protein, human Glutathione S-Transferase pi ERCC1 protein, human Endonucleases Fluorouracil
Topics	Adult Aged Alleles Antineoplastic Agents (therapeutic use) Chemotherapy, Adjuvant DNA-Binding Proteins (genetics) Disease-Free Survival Drug Therapy, Combination Endonucleases (genetics) Female Fluorouracil (therapeutic use) Genotype Glutathione S-Transferase pi (genetics) Humans Male Middle Aged Neoplasm Grading Organoplatinum Compounds (therapeutic use) Oxaliplatin Polymorphism, Single Nucleotide Risk Factors Stomach Neoplasms (drug therapy, genetics, mortality) Treatment Outcome X-ray Repair Cross Complementing Protein 1

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