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

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Abstract

Aim:

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).

Conclusion:

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

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