Prognostic value of cyclooxygenase-2 gene polymorphisms in advanced non-small cell lung cancer patients treated with first-line platinum-based chemotherapy.

Abstract

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. 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. 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). Our study suggested that rs689465 polymorphism could be a prognostic biomarker for advanced NSCLC patients treated with first-line platinum-based chemotherapy.