Genetic polymorphism of GSTP1: prediction of clinical outcome to oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer

J Korean Med Sci. 2010 Jun;25(6):846-52. doi: 10.3346/jkms.2010.25.6.846. Epub 2010 May 24.

Abstract

The aim of this study was to evaluate the predictive value of the polymorphism Glutathione S-transferase P1 (GSTP1) Ile(105)Val on oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. Patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. GSTP1 Ile(105)Val polymorphism was detected by TaqMan-MGB probe allelic discrimination method. Response to treatment was assessed by disease controlled rate. Time to progression, overall survival and toxicities were recorded. Final patient outcomes were as follows: the allele frequencies of GSTP1 were (105)Ile/(105)Ile 52%, (105)Ile/(105)Val 41% and (105)Val/(105)Val 7%. For patients with (105)Ile/(105)Ile and those with at least one (105)Val allele, disease control rate was 39% and 71% (P=0.026), respectively; median time to progression was 4.0 and 7.0 months (P=0.002); median overall survival time was 7.0 and 9.5 months (P=0.002). Neurological toxicity was more frequently occurred in patients with two (105)Ile alleles (P=0.005). In conclusion, patients with at least one (105)Val allele have better prognosis and response to oxaliplatin/5-FU-based regimen as first-line treatment for patients with advanced gastric cancer.

Keywords: Glutathione S-Transferase pi; Oxaliplatin; Polymorphism; Stomach Neoplasms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Disease Progression
  • Female
  • Fluorouracil / therapeutic use*
  • Fluorouracil / toxicity
  • Gene Frequency
  • Genotype
  • Glutathione S-Transferase pi / genetics*
  • Humans
  • Male
  • Middle Aged
  • Organoplatinum Compounds / therapeutic use*
  • Organoplatinum Compounds / toxicity
  • Oxaliplatin
  • Polymorphism, Single Nucleotide*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Survival Analysis
  • Time Factors

Substances

  • Organoplatinum Compounds
  • Oxaliplatin
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Fluorouracil