Single nucleotide polymorphisms and serologic levels of hypoxia-inducible factor1 α and vascular endothelial growth factor are associated with increased risk of oral submucous fibrosis in gutka users among a North Indian population

Abstract

Tissue hypoxia in oral submucous fibrosis (OSMF) induces hypoxia-inducible factor (HIF)-1 α and vascular endothelial growth factor (VEGF), causing angiogenesis. Single nucleotide polymorphisms (SNPs) may predict susceptibility to environmental carcinogens and to development of OSMF, as well as its severity and malignant transformation. This study aimed to determine the serologic levels and frequencies of SNPs of HIF-1 α and VEGF in OSMF. In this prospective pilot study, the frequencies of SNPs of HIF-1 α (C1772 T, G1790 A); VEGF-A 936 C/T; and VEGF-C (rs7664413, rs1485766) in patients with OSMF or oral squamous cell carcinoma (OSCC) and in healthy controls were determined by using polymerase chain reaction (PCR) (n=100 each), and serologic levels were determined by using enzyme-linked immunosorbent assay (ELISA (n=50 each), in a North Indian population. Heterozygous forms of HIF-1 α C1772 T (CT: odds ratio [OR] 5.0; 95% confidence interval [CI] 2.24-11.16; P < .001); HIF-1 α G1790 A (GA: OR 2.8; 95% CI 1.62-5.16; P < .001); and VEGF-C rs1485766 (AC: OR 2.18; 95% CI 1.19-3.99; P < .05) were associated with OSMF. The mean serologic levels of HIF-1 α, VEGF-A, and VEGF-C were significantly raised in patients with OSMF compared with healthy controls (P < .001). The SNPs of HIF-1 α, VEGF-A, and VEGF-C and their serologic levels can act as prognostic biomarkers and aid in the development of specialized anti-HIF-1 α or anti-VEGF drugs for the management and prevention of OSCC in patients with OSMF.