title: Prognostic value of cyclooxygenase-2 gene polymorphisms in advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2) plays an important role in cell apoptosis, angiogenesis and tumor invasion, and over-expression of COX-2 is associated with tumor development and occurrence. The aim of this study is to investigate the association between COX-2 polymorphisms and clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with first-line platinum-based chemotherapy.
  
  
  METHODS
  A total of 190 patients with IIIB or IV NSCLC who received platinum-based chemotherapy were recruited in this study. Four functional COX-2 polymorphisms, including rs689465, rs689466, rs3218625 and rs20417, were genotyped by PCR-based restriction fragment length polymorphism methods. Kaplan-Meier methods were used to compare survival by different genotypes. Cox proportional hazard models were used to identify independently significant variables.
  
  
  RESULTS
  The rs689465 AA genotype was significantly associated with longer overall survival (OS) (13.0 months vs 8.8 months, P = 0.019 for log-rank test; hazard ratio [HR] 0.624; 95% confidence internal [CI] 0.418-0.931) and progression-free survival (5.3 months vs 4.0 months, P = 0.018 for log-rank test; HR 0.627; 95% CI 0.421-0.934) compared with AG or GG genotype, especially in patients with adenocarcinoma (P = 0.002), performance status of 1 (P = 0.009) and stage IV disease (P = 0.012), and treated with gemcitabine-based chemotherapy (P = 0.012). Multivariate regression analysis showed that COX-2 rs689465 polymorphism had a significantly independent prognostic value for OS (P = 0.017, HR = 1.637, 95% CI = 1.093-2.453).
  
  
  CONCLUSIONS
  Our study suggested that rs689465 polymorphism could be a prognostic biomarker for advanced NSCLC patients treated with first-line platinum-based chemotherapy.
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, China.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D002945:Cisplatin / Q000008:administration & dosage; D051546:Cyclooxygenase 2 / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D014747:Vinblastine; D016190:Carboplatin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine
keywords: chemotherapy; cyclooxygenase-2; non-small cell lung cancer; platinum; polymorphism