title: ERCC1 genotype and phenotype in epithelial ovarian cancer identify patients likely to benefit from paclitaxel treatment in addition to platinum-based therapy.
abstract: OBJECTIVE
  To investigate the effect of excision repair cross-complementation group 1 (ERCC1) on treatment response and survival of patients treated with platinum chemotherapy with or without paclitaxel.
  
  
  METHODS
  Tumor samples from epithelial ovarian cancer patients were evaluated for ERCC1 mRNA expression and a single nucleotide polymorphism at codon 118 (C>T). Of 178 patients treated with postoperative platinum-based chemotherapy, 75 were also given paclitaxel. For all of these patients, ERCC1 expression and genotype were analyzed for associations with treatment response and survival.
  
  
  RESULTS
  Among the 103 patients treated with platinum without paclitaxel, the C/C genotype, compared with C/T and T/T, was associated with greater risk of disease progression and death (hazard ratio [HR], 1.95, P = .051; HR, 2.01, P = .033, respectively); high levels of ERCC1 mRNA, compared with low levels, were associated with greater risk of disease progression (HR, 2.41; P = .014). Similarly, when the ERCC1 data were combined, patients with the C/C genotype and high ERCC1 expression had greater risk for disease progression (HR, 3.73; P = .003) compared with those with low expression and non-C/C genotype. However, for the 75 patients treated with platinum plus paclitaxel, the C/C genotype and high ERCC1 expression were not associated with poor prognosis, suggesting that paclitaxel may help to alleviate ERCC1-related platinum resistance.
  
  
  CONCLUSIONS
  Ovarian cancer patients with high ERCC1 expression or the C/C genotype at codon 118 may benefit from the combination of platinum and paclitaxel, while those with low ERCC1 expression or the C/T or T/T genotype may respond well to platinum without paclitaxel.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St, New Haven, CT 06520-8034, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Smith
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.forename: Irene A
authors.initials: IA
authors.lastname: Rigault de la Longrais
authors.forename: Peter
authors.initials: P
authors.lastname: Schwartz
authors.forename: Manuela
authors.initials: M
authors.lastname: Puopolo
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rutherford
authors.forename: Gil
authors.initials: G
authors.lastname: Mor
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D017239:Paclitaxel / Q000627:therapeutic use*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel; D002945:Cisplatin