Associations of VEGFA and KDR single-nucleotide polymorphisms and increased risk and aggressiveness of high-grade gliomas

Abstract

Angiogenesis, induced by the vascular endothelial growth factor A through its ligation to the vascular endothelial growth receptor 2, has been described as a crucial point in high-grade glioma development. The aim of this study was to evaluate the influence of VEGFA–2578C/A, −2489C/T, −1154G/A, −634G/C, and −460C/T, and KDR–604T/C, −271G/A, +1192G/A, and +1719A/T single-nucleotide polymorphisms on risk and clinicopathological aspects of high-grade glioma. This case–control study enrolled 205 high-grade glioma patients and 205 controls. Individuals with VEGFA–2578 CC or CA, VEGFA–1154 GG, VEGFA–634 GC or CC, and VEGFA–460 CT or TT genotypes were under 2.56, 1.53, 1.54, and 1.84 increased risks of high-grade glioma, compared to others, respectively. And 1.61, 2.66, 2.52, 2.53, and 2.02 increased risks of high-grade glioma were seen in individuals with VEGFA–2578 CC plus VEGFA–1154 GG, VEGFA–2578 CC or CA plus VEGFA–634 GC or CC, VEGFA–2578 CC or CA plus VEGFA–460 CT or TT, VEGFA–1154 GG or GA plus VEGFA–634 GC or CC, and VEGFA 634 GC or CC plus VEGFA–460 CT or TT combined genotypes, respectively, when compared to others. The “CAGT” haplotype of KDR single-nucleotide polymorphisms was more common in patients with grade IV than in those with grade III tumors, and individuals carrying this haplotype were at 1.76 increased risk of developing grade IV tumors than others. We present, for the first time, preliminary evidence that VEGFA–2578C/A and VEGFA–1154G/A single-nucleotide polymorphisms increases high-grade glioma risk, and “CAGT” haplotype of the KDR gene alters high-grade glioma aggressiveness and risk of grade IV tumors in Brazil.