Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer population

Pharmacogenomics. 2012 May;13(7):763-70. doi: 10.2217/pgs.12.38.

Abstract

Aim: To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients.

Patients & methods: The study included all patients diagnosed with stage II colon cancer in Denmark in 2003 (698 patients). One paraffin-embedded tissue block from each patient was used for DNA extraction and analysis of the three VEGF SNPs.

Results: The homozygous genotype VEGF -2578 AA had significant effect on time to tumor recurrence (hazard ratio [HR] = 2.01 [95% CI: 1.13-3.56]; p = 0.02) as well as -460TT (HR = 0.50 [95% CI: 0.29-0.89]; p = 0.02). Patients harboring the haplotype combinations ACG,CTC and ACG,ACG displayed a significantly shorter time to tumor recurrence in both univariate (HR = 1.87 [95% CI: 1.21-2.89]; p = 0.008) and multivariate analysis (HR = 1.76 [95% CI: 1.09-2.82]; p = 0.02).

Conclusion: We found that the gene polymorphism in VEGF-A holds prognostic information and should be considered as a potential adjunct in identification of high-risk stage II colon cancer patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Denmark
  • Female
  • Genotype
  • Haplotypes* / genetics
  • Homozygote
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local* / genetics
  • Neoplasm Recurrence, Local* / pathology
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A