Single Nucleotide Polymorphisms (SNP) of the VEGF-gene influence long-term prognosis of oral squamous cell carcinoma

INTRODUCTION: VEGF-SNPs are associated with the incidence of oral squamous cell carcinoma (OSCC). An impact of VEGF-SNPs on prognosis of OSCC patients has not been proven. Therefore, correlations between prognostic parameters of OSCC patients and f VEGF-SNPs were determined. MATERIALS AND METHODS: In a retrospective long- term study, in 120 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. RESULTS: 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 months. A significant increased incidence of OSCC in smokers with the VEGF 2578 A/C and 460 C/T SNP was seen (each P 0.015). 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). DISCUSSION: Possible reciprocal interactions between smoking and VEGF-SNP function were observed. Multi- variate 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. Keywords: Oral Squamous Cell Carcinoma, VEGF Mutation, Single Nucleotide Polymorphisms, Long-term Prognosis