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

Faik G. Uzunoglu MD, Caroline Kaufmann, Harriet Wikman PhD, Cenap Güngör DSc, Benjamin A. Bohn MD, Michael F. Nentwich MD, Matthias Reeh MD, Klaus Pantel, Maximilian Bockhorn PhD, Asad Kutup MD, Oliver Mann PhD, Jakob R. Izbicki, Yogesh K. Vashist MD
Thoracic Oncology
Volume 19, Issue 7 / July , 2012

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Abstract

Purpose

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).

Methods

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^® 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.

Results

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).

Conclusions

VEGFR2 germline polymorphisms predict tumor recurrence and OS in NSCLC.

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