Vascular endothelial growth factor receptor 2 gene polymorphisms as predictors for tumor recurrence and overall survival in non-small-cell lung cancer

Ann Surg Oncol. 2012 Jul;19(7):2159-68. doi: 10.1245/s10434-012-2227-4. Epub 2012 Mar 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Survival Rate
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*

Substances

  • Biomarkers, Tumor
  • Vascular Endothelial Growth Factor Receptor-2