Association of VEGF-A genetic polymorphisms with cancer risk and survival in advanced-stage oral squamous cell carcinoma patients

Abstract

Vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, is overexpressed in a wide variety of human cancers, including oral squamous cell carcinoma (OSCC). In this study, we examined whether individual polymorphisms within VEGF-A gene, rs699947 (-2578C/A), rs1570360 (-1154G/A), rs2010963 (-634G/C), rs3025039 (+936C/T) or their haplotypes are associated with an oral cancer risk and survival. A case-control study was conducted on 114 OSCC patients and control group of 126 individuals without a previous cancer history, all the Caucasian race and the same ethnicity, matched by age and gender. VEGF-A genotypes were analyzed using TaqMan SNP Genotyping Assays, Applied Biosystems. The -1154 GG genotype was significantly associated with the decreased overall survival in OSCC patients (p = 0.010, log rank test). Stratified analysis revealed that in patients with nodal metastases and stage III, -1154 GG genotype was related to worse survival, p = 0.009, p = 0.013, respectively. The multivariate analysis revealed that -1154 GG genotype is an independent adverse factor for survival in the OSCC (HR = 1.899, [1.138-3.168], p = 0.014). The +936 CC genotype was associated with advanced staged OSCC (p = 0.050). The three polymorphisms, -2578, -1154 and -634 were in linkage disequilibrium (LD). The CAG haplotype could be associated with an increased oral cancer risk, OR = 7.967, [1.730-36.689], p = 0.008, while CGG haplotype could be associated with a decreased oral cancer risk, OR = 0.561, [0.326-0.964], p = 0.036. VEGF-A -1154 GG genotype could be considered as a prognostic marker of poor survival in advanced-stage OSCC patients. Haplotypes of VEGF-A gene may be associated with susceptibility to OSCC.