title: TNFRSF1B +676 T>G polymorphism predicts survival of non-small cell lung cancer patients treated with chemoradiotherapy.
abstract: BACKGROUND
  The dysregulation of gene expression in the TNF-TNFR superfamily has been involved in various human cancers including non-small cell lung cancer (NSCLC). Furthermore, functional polymorphisms in TNF-α and TNFRSF1B genes that alter gene expression are likely to be associated with risk and clinical outcomes of cancers. However, few reported studies have investigated the association between potentially functional SNPs in both TNF-α and TNFRSF1B and prognosis of NSCLC patients treated with chemoradiotherapy.
  
  
  METHODS
  We genotyped five potentially functional polymorphisms of TNF-α and TNFRSF1B genes [TNF-α -308 G>A (rs1800629) and -1031 T>C (rs1799964); TNFRSF1B +676 T>G (rs1061622), -1709A>T(rs652625) and +1663A>G (rs1061624)] in 225 NSCLC patients treated with chemoradiotherapy or radiotherapy alone. Kaplan-Meier survival analysis, log-rank tests and Cox proportional hazard models were used to evaluate associations between these variants and NSCLC overall survival (OS).
  
  
  RESULTS
  We found that the TNFRSF1B +676 GG genotype was associated with a significantly better OS of NSCLC (GG vs. TT: adjusted HR = 0.38, 95% CI = 0.15-0.94; GG vs. GT/TT: adjusted HR = 0.35, 95% CI = 0.14-0.88). Further stepwise multivariate Cox regression analysis showed that the TNFRSF1B +676 GG was an independent prognosis predictor in this NSCLC cohort (GG vs. GT/TT: HR = 0.35, 95% CI = 0.14-0.85), in the presence of node status (N2-3 vs. N0-1: HR = 1.60, 95% CI = 1.09-2.35) and tumor stage (T3-4 vs. T0-2: HR = 1.48, 95% CI = 1.08-2.03).
  
  
  CONCLUSIONS
  Although the exact biological function for this SNP remains to be explored, our findings suggest a possible role of TNFRSF1B +676 T>G (rs1061622) in the prognosis of NSCLC. Further large and functional studies are needed to confirm our findings.
authors: Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, Texas 77030, USA.
authors: Xiaoxiang
authors: X
authors: Guan
authors: Zhongxin
authors: Z
authors: Liao
authors: Hongxia
authors: H
authors: Ma
authors: Ji
authors: J
authors: Qian
authors: Zhensheng
authors: Z
authors: Liu
authors: Xianglin
authors: X
authors: Yuan
authors: Daniel
authors: D
authors: Gomez
authors: Ritsuko
authors: R
authors: Komaki
authors: Li-E
authors: LE
authors: Wang
authors: Qingyi
authors: Q
authors: Wei
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D059248:Chemoradiotherapy; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D014409:Tumor Necrosis Factor-alpha