Polymorphisms in p53, GSTP1 and XRCC1 predict relapse and survival of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy

Cancer Chemother Pharmacol. 2009 Oct;64(5):1001-7. doi: 10.1007/s00280-009-0956-2. Epub 2009 Feb 27.

Abstract

Purpose: The aim of this study was to assess whether genetic polymorphisms in p53, glutathione S-transferase P1 (GSTP1), GSTM1, excision repair cross complementing group 1 (ERCC1) and X-ray repair cross-complementing group 1 (XRCC1) genes are associated with clinical outcome of gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy.

Methods: The genetic polymorphisms in p53, GSTP1, GSTM1 (null), ERCC1 and XRCC1 were determined in 102 gastric cancer patients treated with oxaliplatin-based adjuvant chemotherapy using polymerase chain reaction-ligation detection reaction method.

Results: Among the five studied polymorphisms, p53 codon 72 Pro/Pro, GSTP1 codon 105 Ile/Ile, and XRCC1 codon 399 Gln/Gln + Arg/Gln were associated with poor relapse-free survival and overall survival (P < 0.05); and the prognostic effect was retained in the Cox multivariate analysis. Combination analysis with the three polymorphisms using the Kaplan-Meier method and Cox multivariate analysis revealed that the relapse-free and overall survivals significantly increase with the number of favorable genotypes (P < 0.05). No significant association was found between the GSTM1 (null) or the ERCC1 codon 118 genotypes and the clinical outcome (P > 0.05).

Conclusion: Testing for p53 Arg72Pro, GSTP1 Ile105Val, and XRCC1 Arg399Gln polymorphisms may allow identification of gastric cancer patients who will benefit from oxaliplatin-based adjuvant chemotherapy. Selecting specific adjuvant treatments according to the individual genetic background may represent an innovative strategy that warrants prospective studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / therapeutic use*
  • Chemotherapy, Adjuvant*
  • Codon / genetics
  • DNA Repair / drug effects
  • DNA, Neoplasm / biosynthesis
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins / genetics*
  • Female
  • Genes, p53 / genetics*
  • Genotype
  • Glutathione S-Transferase pi / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Polymorphism, Genetic
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics*
  • Survival Analysis
  • Treatment Outcome
  • X-ray Repair Cross Complementing Protein 1

Substances

  • Antineoplastic Agents
  • Codon
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Oxaliplatin
  • GSTP1 protein, human
  • Glutathione S-Transferase pi