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

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% Cl: 1.13-3.56]; p = 0.02) as well as -460TT (HR = 0.50 [95% Cl: 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% Cl: 1.21-2.89]; p = 0.008) and multivariate analysis (HR = 1.76 [95% Cl: 1.09-2.821; 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.