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

Authors


Correspondence: Dr Kämmerer, Peer, W, MD, DMD, Assistant Professor, Department of Oral, Maxillofacial and Plastic Surgery, University Medical Centre, Augustusplatz 2, 55131 Mainz, Germany. Tel.: +00496131 175086, Fax: +00496131/17 6602, E-mail: peer.kaemmerer@gmx.de

Abstract

Introduction

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.

Materials and Methods

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.

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 43.1 months. A significant increased incidence of OSCC in smokers with the VEGF −2578 A/C and −460 C/T SNP was seen (each < 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 < 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. 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.

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