title: Single nucleotide polypmorphisms in ERCC1 are associated with disease progression, and survival in patients with advanced stage ovarian and primary peritoneal carcinoma; a Gynecologic Oncology Group study.
abstract: OBJECTIVE
  This study evaluated common polymorphisms in excision repair cross-complementation group 1 (ERCC1) involved in repair of platinum-induced DNA damage in advanced-stage, epithelial ovarian/peritoneal/tubal cancer (EOC/PPC/FTC) patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy.
  
  
  METHODS
  Pyrosequencing was performed to examine single nucleotide polymorphisms (SNPs) in codon 118 and C8092A in ERCC1 in leukocyte DNA from the Gynecologic Oncology Group phase III protocol, GOG-182. Kaplan-Meier method and adjusted Cox regression modeling were used to examine associations between ERCC1 polymorphisms and progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  The genotype distribution at codon 118 (n=278) in ERCC1 for CC, CT, and TT was 23%, 45% and 32%, and the median OS was 32, 47 and 43 months, respectively. Patients with the CT+TT versus CC genotype in codon 118 in ERCC1 were at a reduced risk of death (hazard ratio [HR]=0.68, 95% confidence interval [CI]=0.49-0.95, p=0.025). The genotype distribution for C8092A in ERCC1 (N=280) was 50%, 42% and 8%, and the median OS was 45, 40 or 30 months for CC, CA and AA, respectively. Women with the CA+AA versus CC genotype in C8092A in ERCC1 had a trend suggesting an increased risk of death (HR=1.29, 95% CI=0.97-1.72, p=0.077).
  
  
  CONCLUSIONS
  The polymorphism in codon 118 in the DNA repair gene ERCC1 was an independent predictor for better survival in EOC/PPC/FTC patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy. The relationship between the C8092A polymorphisms in ERCC1 and survival was modest with an effect size that was not always statistically significant.
authors.affiliation: University of Pittsburgh, Magee-Womens Hospital of UPMC, Pittsburgh PA, USA. tkrivak@mail.magee.edu
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Krivak
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.forename: Chunqiao
authors.initials: C
authors.lastname: Tian
authors.forename: Michael
authors.initials: M
authors.lastname: Bookman
authors.forename: Holly
authors.initials: H
authors.lastname: Gallion
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.forename: Julie A
authors.initials: JA
authors.lastname: Deloia
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D019772:Topotecan / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D004268:DNA-Binding Proteins; D003841:Deoxycytidine; D019772:Topotecan; D004317:Doxorubicin; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel; D000093542:Gemcitabine