The relationship of vascular endothelial growth factor gene polymorphisms and clinical outcome in advanced gastric cancer patients treated with FOLFOX: VEGF polymorphism in gastric cancer

BMC Cancer. 2013 Feb 1:13:43. doi: 10.1186/1471-2407-13-43.

Abstract

Background: The aim of this study is to evaluate the associations between vascular endothelial growth factor (VEGF) Single-nucleotide polymorphisms (SNPs) and clinical outcome in advanced gastric cancer patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX).

Methods: Genomic DNA was isolated from whole blood, and six VEGF (-2578C/A, -2489C/T, -1498 T/C, -634 G/C, +936C/T, and +1612 G/A) gene polymorphisms were analyzed by PCR. Levels of serum VEGF were measured using enzyme-linked immunoassays.

Results: Patients with G/G genotype for VEGF -634 G/C gene polymorphism showed a lower response rate (22.2%) than those with G/C or C/C genotype (32.3%, 51.1%; P = 0.034). Patients with the VEGF -634 G/C polymorphism G/C + C/C genotype had a longer progression free survival (PFS) of 4.9 months, compared with the PFS of 3.5 months for those with the G/G (P = 0.043, log-rank test). By multivariate analysis, this G/G genotype of VEGF -634 G/C polymorphism was identified as an independent prognostic factor (Hazard ratio 1.497, P = 0.017).

Conclusion: Our data suggest that G/G genotype of VEGF -634 G/C polymorphism is related to the higher serum levels of VEGF, and poor clinical outcome in advanced gastric cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Chi-Square Distribution
  • Disease-Free Survival
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorouracil / administration & dosage
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Organoplatinum Compounds / administration & dosage
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Prospective Studies
  • Stomach Neoplasms / blood
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / blood
  • Vascular Endothelial Growth Factor A / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Organoplatinum Compounds
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol