XRCC1 and GSTP1 polymorphisms and prognosis of oxaliplatin-based chemotherapy in colorectal cancer: a meta-analysis

Cancer Chemother Pharmacol. 2013 Mar;71(3):733-40. doi: 10.1007/s00280-012-2067-8. Epub 2013 Jan 9.

Abstract

Purpose: Genetic variations are related to individual differences of DNA repair ability and drug metabolism, which can greatly influence prognosis of antineoplastic agents, such as oxaliplatin. The aim was to explore the influences of X-ray repair cross-complementing 1(XRCC1) and Glutathione S-transferase P1 (GSTP1) genetic variants on prognosis of oxaliplatin-based chemotherapy in colorectal cancer patients.

Methods: We performed a meta-analysis including 13 original studies with a total number of 1,234 patients in advanced or metastatic colorectal cancer. Tumor responses [complete response, partial response, stable disease (SD) and progressive disease (PD)] and progression-free survival were estimated.

Results: Our results showed that XRCC1 Arg399Gln polymorphism was significantly associated with tumor chemotherapy when SD or PD was considered as non-response [risk ratio (RR) = 1.29; 95% confidence intervals (CI): 1.05-1.60; P = 0.02]. No significant association was found between GSTP1 Ile105 Val polymorphism and tumor response (RR = 0.63; 95% CI: 0.35-1.14; P = 0.13). In addition, our results also showed that there was no significant association between XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes and hazard ratio for progression-free survival (Hazards ratio = 1.04 and 1.92; 95% CI: 0.75-1.43 and 0.62-1.37; P = 0.826 and 0.677, respectively).

Conclusion: In our meta-analysis, XRCC1 Arg399Gln polymorphism may be a valuable genetic marker for oxaliplatin-based chemotherapy in colorectal cancer, and the results still need further confirmation.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Confidence Intervals
  • DNA Repair
  • DNA-Binding Proteins / genetics*
  • Disease-Free Survival
  • Genetic Markers
  • Genotype
  • Glutathione S-Transferase pi / genetics*
  • Organoplatinum Compounds / pharmacokinetics
  • Organoplatinum Compounds / therapeutic use*
  • Oxaliplatin
  • Polymorphism, Genetic / genetics
  • Prognosis
  • Proportional Hazards Models
  • Risk Assessment
  • X-ray Repair Cross Complementing Protein 1

Substances

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