VEGF-460T→C polymorphism and its association with VEGF expression and outcome to FOLFOX-4 treatment in patients with colorectal carcinoma

The -460T -> C polymorphism of vascular endothelial growth factor (VEGF) gene significantly increases its promoter activity. A pilot study was conducted to assess the influence of this polymorphism on clinicopathological features of patients with colorectal carcinoma. In total, 228 patients were enrolled, including 100 with stage II/III colorectal carcinoma receiving curative surgery and 128 with metastatic disease. An excellent correlation in VEGF -460 genotypes based on white blood cells and tumor tissues existed, but there was no between-group difference in patients with or without colorectal carcinoma. A marked increase in intratumor and circulating VEGF levels were observed in patients with the T/C or C/C genotypes (P<0.01), which was associated with increased extent of invasion, nodal involvement, poor histological differentiation, subsequent metastasis and shorter survival in stage II/III patients treated with curative surgery (P<0.01). For patients with metastatic disease, this polymorphism was associated with a lower response rate to FOLFOX-4 (P=0.03) and shorter survival (P<0.001). By multivariate analysis, this polymorphism was identified as an independent prognostic factor (P=0.01). These data suggest that -460T -> C polymorphism of VEGF gene, by increasing VEGF expression and subsequent angiogenesis, could be a key determinant for increased tumor recurrence and a poor prognosis of patients with colorectal carcinoma. However, this study is exploratory and is not adjusted for multiple comparisons, requiring independent replication. The Pharmacogenomics Journal (2011) 11, 227-236; doi:10.1038/tpj.2010.48; published online 8 June 2010