Vascular Endothelial Growth Factor Receptor 2 Gene Polymorphisms as Predictors for Tumor Recurrence and Overall Survival in Non-Small-Cell Lung Cancer

VEGFR-2 gene displays several functional germline polymorphisms with impact on VEGFR-2 mediated angiogenesis. Our purpose was to evaluate VEGFR-2 polymorphisms as prognostic markers for tumor recurrence and overall survival (OS) in non-small-cell lung cancer (NSCLC). In total, 209 Caucasian patients who had been surgically treated for NSCLC between 1996 and 2010 were included in this study. Genotyping of peripheral blood cells was performed by TaqMan(A (R)) genotyping assays or polymerase chain reaction for five VEGFR-2 polymorphisms. Chi- square test, Kaplan-Meier estimator, and Cox regression hazard model were used to assess the prognostic value of VEGFR-2 polymorphisms. VEGFR-2+4422 (AC)(10-14) polymorphism was identified as a positive prognostic marker for time to metastasis (11/12 vs. 11/11 (AC) repeats: hazard ratio (HR), 0.28; 95% confidence interval (CI), 0.11-0.75; p = 0.012) and OS (11/12 vs. 11/11 (AC) repeats: HR, 0.41; 95% CI, 0.21-0.82; p = 0.012) in squamous cell carcinoma. For adenocarcinoma, VEGFR-2-906 C > T (C/T vs. CC: HR, 0.19; 95% CI, 0.43-0.82; p = 0.027) and VEGFR-2-271 G > A (G/A vs. G/G: HR, 0.25; 95% CI, 0.07-0.86; p = 0.027) predicted longer time to local recurrence and VEGFR-2-906 C > T was a predictor for better OS (T/T vs. C/C: HR, 0.28; 95% CI, 0.09-0.84; p = 0.024). VEGFR2 germline polymorphisms predict tumor recurrence and OS in NSCLC.