title: Homozygous GNAS 393C-allele carriers with locally advanced esophageal cancer fail to benefit from platinum-based preoperative chemoradiotherapy.
abstract: BACKGROUND
  Currently, patients with locally advanced esophageal cancer receive neoadjuvant chemoradiotherapy but only about half of these patients benefit from this treatment. GNAS T393C has been shown to predict the postoperative course in solid tumors and may therefore be useful for treatment stratification. The aim of the present study was to determine if the single-nucleotide polymorphism GNAS T393C can be used for treatment stratification in esophageal cancer patients.
  
  
  METHODS
  A total of 596 patients underwent surgical resection for esophageal carcinoma from 1996 to 2008; 279 patients received chemoradiotherapy prior to surgery (RTX-SURG group). All patients and a reference group of 820 healthy White individuals were genotyped for GNAS T393C.
  
  
  RESULTS
  The 5-year-survival rate for the 317 patients who underwent esophagectomy as initial treatment (SURG group) was 57 % for homozygous C-allele carriers (n = 99) and 43 % for T-allele carriers (n = 218; log- rank test p = 0.025). Multivariate analysis revealed the GNAS T393C genotype (p = 0.034), pT (p < 0.001), pN (p < 0.001) and age (p < 0.001) as prognostic of survival. Homozygous C-allele carriers with a locally advanced tumor stage (cT3/T4, n = 129) in the SURG group had a 5-year survival rate of 37 %, which, remarkably, exceeded the 5-year survival rate of 30 % for the entire RTX-SURG group (n = 279). In the RTX-SURG group, the GNAS T393C genotype did not show any prognostic significance.
  
  
  CONCLUSIONS
  Patients with a locally advanced esophageal cancer and an homozygous GNAS 393C genotype do not benefit from platinum-based neoadjuvant chemoradiotherapy, indicating that these patients should be treated by alternative treatment strategies.
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany, halakus@ucsd.edu.
authors.forename: Hakan
authors.initials: H
authors.lastname: Alakus
authors.forename: Elfriede
authors.initials: E
authors.lastname: Bollschweiler
authors.forename: Arnulf H
authors.initials: AH
authors.lastname: Hölscher
authors.forename: Ute
authors.initials: U
authors.lastname: Warnecke-Eberz
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Frazer
authors.forename: Olivier
authors.initials: O
authors.lastname: Harismendy
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lowy
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Mönig
authors.forename: Pascal M
authors.initials: PM
authors.lastname: Eberz
authors.forename: Martin
authors.initials: M
authors.lastname: Maus
authors.forename: Uta
authors.initials: U
authors.lastname: Drebber
authors.forename: Winfried
authors.initials: W
authors.lastname: Siffert
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzger
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy / Q000401:mortality*; D002864:Chromogranins; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000401:mortality*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010984:Platinum / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D002864:Chromogranins; D010984:Platinum; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs