title: ERCC1 C8092A (rs3212986) polymorphism as a predictive marker in esophageal cancer patients treated with cisplatin/5-FU-based neoadjuvant therapy.
abstract: OBJECTIVE
  At present, no consensus exists on the beneficial effect of preoperative cisplatin/5-fluorouracil (5-FU)-based chemotherapy versus primary surgery in the management of patients with esophageal cancer. The aim of this study was to evaluate the impact of some relevant genetic polymorphisms, within drug-related and DNA repair genes, on the clinical outcome of esophageal cancer patients subjected to cisplatin/5-FU-based neoadjuvant treatment.
  
  
  METHODS
  DNA from 143 esophageal cancer patients, 63 receiving neoadjuvant therapy and 80 receiving primary surgery, was analyzed for the following polymorphisms: the GSTM1 null, GSTT1 null, and GSTP1 Ile105Val (rs16953) in glutathione S-transferase (GST) family, 2 in thymidylate synthase (TS) gene, and the ERCC1 Asn118Asn (rs11615), ERCC1 C8092A (rs3212986), XPD/ERCC2 Asp312Asn (rs1799793), and XPD/ERCC2 Lys751Gln (rs13181) of the nucleotide excision repair pathway.
  
  
  RESULTS
  We found that the ERCC1 rs3212986, although not associated with therapeutic response, is an independent predictive marker of better outcome in a cisplatin/5-FU-based neoadjuvant setting (hazard ratio: 0.38, 95% confidence interval: 0.2-0.73, P=0.008). In contrast, no association with clinical outcome was observed for this polymorphism in the primary surgery group.
  
  
  CONCLUSIONS
  Our study indicates the ERCC1 rs3212986 as a predictive marker in the cisplatin/5-FU-based neoadjuvant setting, and also suggests its use as a marker to select the appropriate therapeutic approach in esophageal cancer patients.
authors: aImmunology and Molecular Oncology Unit bOncological Surgery Unit, Veneto Institute of Oncology IOV-IRCCS Departments of cLaboratory Medicine dSurgical Sciences, Oncology and Gastroenterology, University of Padova, Padova, Italy.
authors: Enrica
authors: E
authors: Rumiato
authors: Francesco
authors: F
authors: Cavallin
authors: Elisa
authors: E
authors: Boldrin
authors: Matteo
authors: M
authors: Cagol
authors: Rita
authors: R
authors: Alfieri
authors: Daniela
authors: D
authors: Basso
authors: Carlo
authors: C
authors: Castoro
authors: Ermanno
authors: E
authors: Ancona
authors: Alberto
authors: A
authors: Amadori
authors: Alberto
authors: A
authors: Ruol
authors: Daniela
authors: D
authors: Saggioro
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000601:surgery; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage* / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use; D005819:Genetic Markers; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D020360:Neoadjuvant Therapy; D011110:Polymorphism, Genetic; D013940:Thymidylate Synthase / Q000235:genetics; D016896:Treatment Outcome; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D002945:Cisplatin; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005472:Fluorouracil; D005819:Genetic Markers; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D013940:Thymidylate Synthase; D051759:Xeroderma Pigmentosum Group D Protein; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C071447:ERCC1 protein, human; C497292:ERCC2 protein, human