Association of specific single nucleotide variants (SNVs) in the promoter and 3′-Untranslated region of Vascular Endothelial growth factor (VEGF) gene with risk and higher tumour grade of head and neck cancers

Abstract

BackgroundHead and Neck Cancers (HNCs)comprise one of the most frequent cancers in South-Asian region. Vascular Endothelial Growth Factor (VEGF) has a potent role in tumorigenesis and metastasis. Certain common single nucleotide variants (SNVs) in the highly polymorphic VEGF gene are correlated with variations in VEGF functions. The data for these SNVs in HNCs is scarce for South Asian populations.The present study addresses this shortfall. It investigates the association of two VEGF SNVs, −2578C/A (rs699947) in the promoter region and + 936C/T (rs3025039) in 3′-UTR, with the risk of HNCs and tumour characteristics. MethodsThe study comprised 323 participants with 121 HNC patients and 202 controls. Germline DNA was isolated from peripheral blood samples. PCR-RFLP methods were optimized and validated by Sanger sequencing. After Hardy-Weinberg evaluation, the independent associations were analyzed under the assumptions of different genetic models. The χ2 test of independence or Fisher’s Exact test (significant p-values at < 0.05) were performed and ORs (odds ratios) with 95% confidence interval were tabulated. ResultsVEGF −2578 A-allele, CA + AA, and AA genotypes had significant protective association against HNCs. The respective ORs were: 0.651 (0.469–0.904), 0.613 (0.381 – 0.985), and 0.393 (0.193–0.804). VEGF + 936 T-allele, CT, and CT + TT genotypes had significantly increased susceptibility for HNCs. The respective ORs were 1.882 (1.001 – 3.536), 2.060 (1.035 – 4.102), and 2.023 (1.032 – 3.966). Additionally, VEGF + 936 CT and CT + TT genotypes showed significant associations with higher tumour grade (p-values < 0.029, and < 0.037, respectively). ConclusionThe present study is the foremost report of independent and unique associations of the investigated VEGF SNVs with HNCs.