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

Abstract

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.

Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy

“…First, the study could not address the mechanism of how the VEGF polymorphisms influence the survival outcomes of lung cancer patients. Previous study demonstrated a good correlation between TC/CC genotypes of the VEGF -460 T > C polymorphism and increased serum VEGF levels in colorectal cancer patients [21]. An increased serum VEGF expression was also observed in ovarian cancer patients carrying -634 C allele [22].…”

Common Polymorphisms in Angiogenesis

“…In colorectal cancer, VEGF promoter polymorphisms predict response and time to progression with anti-VEGF therapy (Pander et al 2010). However, promoter polymorphisms have similar predictive power with chemotherapy regimens lacking an anti-VEGF component (Chen et al 2010a). Similar results are obtained in lung cancer (Heist et al 2008).…”

Role of Vascular Endothelial Growth Factor (VEGF) and VEGF-R Genotyping in Guiding the Metastatic Process in pT4a Resected Gastric Cancer Patients

“…A correlation between the presence of a specific allele on a polymorphic site and the expression of the respective protein has been previously documented for VEGF [22], [23]. SNPs in regulatory sequences, such as introns and 5′ and 3′ UTRs, have been shown to alter mRNA stability [24], [25] processing efficiency [26], isoform expression [27], [28] and localization [29].…”