title: A polymorphic -844T/C in FasL promoter predicts survival and relapse in non-small cell lung cancer.
abstract: OBJECTIVE
  Fas ligand (FasL) -844T/C polymorphism (rs763110) has a demonstrated association with lung cancer risk. FasL -844CC with higher FasL expression has been suggested to contribute to tumor progression via immune escape. However, the impact of FasL -844T/C polymorphism on the clinical outcome of non-small cell lung cancer (NSCLC) remains to be identified.
  
  
  METHODS
  A total of 385 adjacent normal lung tissues from patients with NSCLC were collected to determine FasL -844T/C polymorphism by PCR-based restriction fragment length polymorphism. FasL mRNA and protein expression in lung tumors were evaluated by real-time PCR and immunohistochemistry. The prognostic value of FasL -844T/C polymorphism on survival and relapse was determined by Kaplan-Meier analysis and Cox proportional hazards models.
  
  
  RESULTS
  The FasL -844CC genotype had higher prevalence in those with advanced tumors than in those with early tumors (P = 0.008). In addition, patients with the FasL -844CC genotype were more prone to tumor relapse than those with the FasL -844TT+TC genotype (62.1% vs. 37.9%, P = 0.001). Multivariate Cox regression analysis showed that patients with the FasL -844CC genotype had poorer survival in terms of overall survival (OS) and relapse-free survival (RFS) than those with the FasL -844TT+TC genotype (24.1 vs. 42.8 months for OS, HR = 1.455, P = 0.004; 15.4 vs. 31.4 months for RFS, HR = 1.710, P < 0.001).
  
  
  CONCLUSIONS
  FasL -844T/C polymorphism may predict survival and relapse in NSCLC. We suggest that FasL may be a molecular target for immunotherapeutic interventions to improve the clinical outcome of patients with NSCLC. This finding should be validated by another investigative group.
authors.affiliation: Institute of Medical & Molecular Toxicology, School of Medicine, Institute of Medicine, and School of Public Health, Chung Shan Medical University, Changhua, Taiwan, ROC.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Sung
authors.forename: Yao-Chen
authors.initials: YC
authors.lastname: Wang
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
authors.forename: Ming-Ching
authors.initials: MC
authors.lastname: Lee
authors.forename: Kun-Tu
authors.initials: KT
authors.lastname: Yeh
authors.forename: Lee
authors.initials: L
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Wang
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Huei
authors.initials: H
authors.lastname: Lee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D053222:Fas Ligand Protein / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D053222:Fas Ligand Protein; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53