Vascular endothelial growth factor polymorphisms as effect modifiers of oral squamous cell carcinoma risk: A systematic review and meta-analysis

Abstract

Smoking is one of the main risk factors for the development of oral squamous cell carcinoma (OSCC). Smoking may affect single-nucleotide polymorphism (SNP)-dependent vascular endothelial growth factor (VEGF)-induced angiogenic activity. Therefore, we systematically reviewed the published VEGF-SNP genotype data of OSCC patients and healthy individuals and performed a meta-analysis comparing the VEGF-SNP genotypes of smoking and non-smoking patients in association with OSCC incidence. Prospective and retrospective studies on the clinical comparison of OSCC patients with different VEGF-SNP genotypes were reviewed. The meta-analysis re-pooled studies of smoking and non-smoking OSCC patients with different VEGF-SNPs between 2006 and 2014. The identified articles were reviewed and those reporting pertinent information, assignment to smoking and non-smoking patient groups and sufficient data for estimation of an odds ratio (OR) with a 95% confidence interval (CI) were selected for the meta-analysis. Pooled ORs and CIs for the comparison of SNP distribution in the smoking and non-smoking subgroups were calculated and compared using the random-effects model. A total of 7 studies were included in the systematic review, which was followed by a meta-analysis using 3 pertinent studies. The reviewed studies reported discrepant findings, with differences between Asian and European patients. The meta-analysis demonstrated marginal but not statistically significant differences, suggesting that specific VEGF-SNPs may be OSCC risk modifiers for smokers, depending on the ethnic background. The performed meta-analysis suggested an increased OSCC risk for smokers carrying specific VEGF-genotypes, although the calculated data did not reach the level of significance. However, data have to be interpreted with caution due to the limited sample size. Therefore, further studies, including larger patient samples, are mandatory.

Keywords: meta-analysis; oral squamous cell carcinoma; single-nucleotide polymorphisms; smoking; vascular endothelial growth factor.

Figure 1.

Flowchart of the study selection process for the meta-analysis and systematic review. VEGF, vascular endothelial growth factor; SNPs, single-nucleotide polymorphisms; OSCC, oral squamous cell carcinoma.

Figure 2.

Forest plot of ORs for the association of the −460 C/G, +936 C/T, −1154 G/A and −2578 C/A SNPs in the vascular endothelial growth factor gene, with susceptibility to oral squamous cell carcinoma and smoking status. OR, odds ratio; CI, confidence interval; SNP, single-nucleotide polymorphism.