Strong and Significant Associations of Single Nucleotide Variants (SNVs) in the Promoter and 3'-Untranslated Region (3'-UTR) of Vascular Endothelial Growth Factor (VEGF) Gene with Head and Neck Cancers

Abstract

BackgroundVascular Endothelial Growth Factor (VEGF) has a potent role in tumorigenesis and metastasis. However, data for the role of common single nucleotide variants (SNVs) in the highly polymorphic VEGF gene in head and neck cancers (HNCs) is limited in general and unavailable in South Asian populations. The present study addresses this shortfall. It investigates the association of two VEGF SNVs, -2578 C/A (rs699947) in the promoter region and +936 C/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 by applying genetic models. The {chi}2 test of independence or Fishers Exact test (significant p-values at <0.05) were performed and ORs (odds ratios) with 95% confidence interval were tabulated. ResultsVEGF -2578 A-allele, A-carrier 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 T-carrier 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 T-carrier genotypes showed significant associations with higher tumour grade (p-value <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.