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VEGF and VEGFR polymorphisms affect clinical outcome in advanced renal cell carcinoma patients receiving first-line

M Scartozzi1, M Bianconi, L Faloppi

  • 1Department of Clinical Oncology, AOU Ospedali Riuniti, Polytechnic University of the Marche Region, Ancona, Italy. marioscartozzi@gmail.com

British Journal of Cancer
|March 21, 2013
PubMed
Abstract

Insights

Specific genetic variations in VEGF and VEGFR may predict treatment response in metastatic renal cell carcinoma (mRCC) patients receiving sunitinib. Certain polymorphisms are linked to poorer progression-free survival and overall survival outcomes.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • Sunitinib is a key treatment for renal cell carcinoma (RCC).
  • Predictive biomarkers for sunitinib treatment selection are currently lacking.
  • This study investigates the role of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) gene polymorphisms in predicting clinical outcomes for metastatic RCC (mRCC) patients.

Purpose of the Study:

  • To assess the predictive value of VEGF and VEGFR single-nucleotide polymorphisms (SNPs) for treatment response in mRCC patients.
  • To correlate specific VEGF and VEGFR SNPs with progression-free survival (PFS) and overall survival (OS) in patients treated with sunitinib.

Main Methods:

  • Genotyping of VEGF and VEGFR SNPs was performed on 84 tumor samples from mRCC patients receiving first-line sunitinib.
  • Progression-free survival (PFS) and overall survival (OS) data were collected and analyzed.
  • Statistical analysis, including multivariate analysis, was used to determine the significance of SNP associations with survival outcomes.

Main Results:

  • Median PFS was 8.22 months and median OS was 32.13 months.
  • Several VEGF SNPs (rs833061, rs699947, rs2010963) and one VEGFR SNP (rs6877011) showed significant associations with both PFS and OS.
  • Multivariate analysis identified rs833061, rs2010963, and rs68877011 as significant predictors for PFS, and rs833061 and rs68877011 as independent predictors for OS.

Conclusions:

  • Specific VEGF and VEGFR polymorphisms (TT at rs833061, CC at rs699947, CC at rs2010963, and CG at rs6877011) are associated with worse PFS and OS in mRCC patients treated with sunitinib.
  • These findings suggest that VEGF and VEGFR polymorphisms could serve as potential biomarkers for predicting sunitinib efficacy in mRCC.

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