title: The T393C polymorphism of GNAS1 is a predictor for relapse and survival in resectable non-small cell lung cancer.
abstract: BACKGROUND
  The GNAS1 T393C single nucleotide polymorphism (T393C-SNP) correlates with Gαs mRNA stability and protein expression and augmented apoptosis. Genetic germ line variations as stable and reproducible markers potentially serve as prognostic marker in oncology. The aim of this study was to evaluate the potential prognostic value of T393C-SNP in complete resected non-small cell lung cancer (NSCLC).
  
  
  METHODS
  In total 163 Caucasian patients, who had been surgically treated for NSCLC between 1998 and 2010, were included in this study. Genotyping of peripheral blood cells was performed by polymerase chain reaction and digestion using the restriction enzyme FokI. The T393C-SNP was correlated with clinic-pathological parameters and survival. Chi-square test, Kaplan-Meier estimator and cox regression hazard model were used to assess the prognostic value of the T393C-SNP.
  
  
  RESULTS
  C-allele carriers had a higher recurrence rate (p=0.018) and a shorter disease-free survival compared to homozygous T-allele carriers (12.26 months vs. 44.65 months, p=0.009). The overall survival in homozygous C allele carriers was shorter (19.10 months vs. 53.95 months, p=0.019). Multivariate Cox regression identified the CC genotype as a negative independent prognostic factor for recurrence (hazard ratio 2.36, p=0.007) and survival (hazard ratio 2.51, p=0.008).
  
  
  CONCLUSIONS
  Determination of T393C-SNP preoperatively potentially allows allocation of NSCLC patients into different risk profiles and may influence the therapeutic strategy.
authors.affiliation: Department of General, Visceral and Thoracic Surgery, University Medical Centre of Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
authors.forename: Faik Güntac
authors.initials: FG
authors.lastname: Uzunoglu
authors.forename: Asmus
authors.initials: A
authors.lastname: Heumann
authors.forename: Safije
authors.initials: S
authors.lastname: Musici
authors.forename: Asad
authors.initials: A
authors.lastname: Kutup
authors.forename: Alexandra
authors.initials: A
authors.lastname: Koenig
authors.forename: Nadine
authors.initials: N
authors.lastname: Roch
authors.forename: Adriana
authors.initials: A
authors.lastname: Thomssen
authors.forename: Thorsten
authors.initials: T
authors.lastname: Dohrmann
authors.forename: Tung Yu
authors.initials: TY
authors.lastname: Tsui
authors.forename: Oliver
authors.initials: O
authors.lastname: Mann
authors.forename: Jakob Robert
authors.initials: JR
authors.lastname: Izbicki
authors.forename: Yogesh Kumar
authors.initials: YK
authors.lastname: Vashist
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000601:surgery; D016009:Chi-Square Distribution; D002864:Chromogranins; D018572:Disease-Free Survival; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs