title: Polymorphisms in apoptosis-related genes and survival of patients with early-stage non-small-cell lung cancer.
abstract: OBJECTIVE
  This study was conducted to determine the association between single-nucleotide polymorphisms (SNPs) in apoptosis-related genes and survival outcomes of patients with early-stage non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Three hundred ten consecutive patients with surgically resected NSCLC were enrolled. Twenty-five SNPs in 17 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay. The genotype associations with overall survival (OS) and disease-free survival (DFS) were analyzed.
  
  
  RESULTS
  Three SNPs (TNFRSF10B rs1047266, TNFRSF1A rs4149570, and PPP1R13L rs1005165) were significantly associated with survival outcomes on multivariate analysis. When the three SNPs were combined, OS and DFS were decreased as the number of bad genotypes increased (P (trend) for OS and DFS = 7 × 10(-5) and 1 × 10(-4), respectively). Patients with one bad genotype, and patients with two or three bad genotypes had significantly worse OS and DFS compared with those with no bad genotypes [adjusted hazard ratio (aHR) for OS = 2.27, 95% confidence interval (CI) = 1.22-4.21, P = 0.01, aHR for DFS = 1.74, 95% CI = 1.08-2.81, P = 0.02; aHR for OS = 4.11, 95% CI = 2.03-8.29, P = 8 × 10(-5); and aHR for DFS = 2.89, 95% CI = 1.64-5.11, P = 3 × 10(-4), respectively].
  
  
  CONCLUSIONS
  Three SNPs in apoptosis-related genes were identified as possible prognostic markers of survival in patients with early-stage NSCLC. The SNPs, and particularly their combined genotypes, can be used to identify patients at high risk for poor disease outcome.
authors.affiliation: Department of Thoracic Surgery, Kyungpook National University Hospital, Daegu, Korea.
authors.forename: Eung Bae
authors.initials: EB
authors.lastname: Lee
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Seung Soo
authors.initials: SS
authors.lastname: Yoo
authors.forename: Yi Young
authors.initials: YY
authors.lastname: Choi
authors.forename: Hyo-Gyoung
authors.initials: HG
authors.lastname: Kang
authors.forename: Sukki
authors.initials: S
authors.lastname: Cho
authors.forename: Sung-Ick
authors.initials: SI
authors.lastname: Cha
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Tae-In
authors.initials: TI
authors.lastname: Park
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
authors.forename: Rang-Woon
authors.initials: RW
authors.lastname: Park
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Jheon
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Jung
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; C119612:PPP1R13L protein, human; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D047888:Receptors, Tumor Necrosis Factor, Type I; D012097:Repressor Proteins; C505639:TNFRSF10B protein, human; C506235:TNFRSF1A protein, human