title: Predictors of survival in never-smokers with non-small cell lung cancer: a large-scale, two-phase genetic study.
abstract: OBJECTIVE
  Lung cancer in never-smokers (LCINS) is increasingly recognized as a distinct disease from that in ever-smokers owing to substantial differences in etiology, clinical characteristics, and prognosis. Therefore, we aimed to identify prognostic markers specific for LCINS.
  
  
  METHODS
  First, 11,930 single-nucleotide polymorphisms (SNP) in 904 inflammation-related genes were genotyped, and their associations with overall survival in 411 patients with LCINS at MD Anderson Cancer Center were analyzed. Next, validation of the top 27 SNPs in 311 patients with LCINS at Mayo Clinic was conducted.
  
  
  RESULTS
  Three SNPs (IL17RA:rs879576, BMP8A:rs698141, and STY:rs290229) were validated (P < 0.05), and two SNPs (CD74:rs1056400 and CD38:rs10805347) reached borderline significance (P = 0.08) in the Mayo Clinic population. We validated a survival-tree created in the MD Anderson population exploring gene-gene interactions in the Mayo Clinic population. This survival-tree stratified patients into subsets with significantly different risks of death: patients with the rs1056400_GG/rs698141_GA + AA genotype had significantly higher risk of death in both MD Anderson (HR:2.32, 95%CI: 1.58-3.41) and Mayo (HR:1.97, 95%CI: 1.11-3.50) populations compared with those with the rs1056400_GG/rs698141_GG or rs1056400_GA + AA genotype. We evaluated these five SNPs in 996 ever-smokers from MD Anderson and found no significant associations.
  
  
  CONCLUSIONS
  Our study provides strong evidence that inflammation-related genetic variations can affect clinical outcomes in LCINS, which may lead to significant biologic insight into these outcomes.
authors.affiliation: Department of Epidemiology, Thoracic/Head & Neck Medical Oncology, and Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Pu
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Michelle A T
authors.initials: MA
authors.lastname: Hildebrandt
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012907:Smoking