Associations between single-nucleotide polymorphisms of the VEGF gene and long-term prognosis of oral squamous cell...

Functional polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) are associated with the incidence of oral squamous cell carcinoma (OSCC). An impact of VEGF-SNPs on prognosis of OSCC patients seems possible. Therefore, correlations between prognostic parameters of OSCC patients and five VEGF-SNPs were determined.

In a retrospective long-term study, in 113 OSCC patients that underwent curative resections, five VEGF-SNPs (-1154 G/A, +405 G/C, +936 C/T, -2578 C/A, and -460 C/T) were analyzed. Associations between SNPs and prognosis (incidence of local recurrent disease, second cancer, metastases, death, total disease-free survival) were examined.

After a mean follow-up time of 57.6 months, 32 patients had local recurrences; 15 patients had second cancer, 15 patients metastases, and 23 patients died. The mean disease-free survival was 43.1 months. A significant increased incidence of OSCC in smokers with the VEGF -2578 A/C and -460 C/T SNP was seen (each P < 0.0001). In univariate analysis, patients with advanced OSCCs (T > 2 or N > 0) together with the -1154 A/A allele had a significant worse survival and a worse disease-free survival (both P < 0.04). The same was seen for the +405 G/G SNP (both P = 0.002). In multivariate analysis, only the negative influence of the +405 G/G SNP on survival in advanced OSCCs (T > 2) could be confirmed (P = 0.002).

Possible reciprocal interactions between smoking and VEGF-SNP function were observed. Multivariate analysis confirmed the VEGF +405 G/G genotype to be associated with poor survival in advanced OSCCs; a further use of this haplotype as biomarker has to be discussed.