title: ERCC1 and ERCC2 polymorphisms predict clinical outcomes of oxaliplatin-based chemotherapies in gastric and colorectal cancer: a systemic review and meta-analysis.
abstract: OBJECTIVE
  Nucleotide excision repair (NER) modulates platinum-based chemotherapeutic efficacy by removing drug-produced DNA damage. To summarize published data on the association between polymorphisms of NER genes (ERCC1 and ERCC2) and responses to oxaliplatin-based chemotherapies, we carried out a meta-analysis of gastric and colorectal cancer for commonly studied polymorphisms ERCC1 rs11615C>T and ERCC2 rs13181T>G.
  
  
  METHODS
  In 17 previously published studies, 1,787 cancer patients were treated with the oxaliplatin-based regimen. Primary outcomes included therapeutic response (TR; i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS), and overall survival (OS). We calculated OR or HR with 95% CIs to estimate the risk or hazard.
  
  
  RESULTS
  We found consistent and clinically substantial risk or hazard for TR, PFS, and OS in the oxaliplatin-treated gastric and colorectal cancer patients with an ethnic discrepancy. For ERCC1 rs11615C>T, the T allele was associated with reduced response and poor PFS and OS in Asians (TR: OR = 0.53 and 95% CI = 0.35-0.81; PFS: HR = 1.69 and 95% CI = 1.05-2.70; and OS: HR = 2.03 and 95% CI = 1.60-2.59). For ERCC2 rs13181T>G, the G allele was associated with reduced response and poor PFS and OS in Caucasians (TR: OR = 0.56 and 95% CI = 0.35-0.88; PFS: HR = 1.41 and 95% CI = 1.02-1.95; and OS: HR = 1.42 and 95% CI = 1.11-1.81).
  
  
  CONCLUSIONS
  NER ERCC1 rs11615C>T and ERCC2 rs13181T>G polymorphisms are useful prognostic factors in oxaliplatin-based treatment of gastric and colorectal cancer. Larger studies and further clinical trials are warranted to confirm these findings.
authors.affiliation: Department of Epidemiology, MD Anderson Cancer Center, The University of Texas, Houston, Texas 77030, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
authors.forename: Jingrong
authors.initials: J
authors.lastname: Yan
authors.forename: Eva
authors.initials: E
authors.lastname: Martinez-Balibrea
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jacques
authors.initials: J
authors.lastname: Robert
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Wei-Shu
authors.initials: WS
authors.lastname: Wang
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Etienne-Grimaldi
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000483:Alleles; D000970:Antineoplastic Agents / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics*; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D012306:Risk; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human