Association between functional EGF+61polymorphism and glioma risk

Abstract

Epidermal growthf actor (EGF) plays a critical role in cancer. A polymorphism in the EGF gene (EGF+61) may influence its expression and contribute to cancer predisposition and aggressiveness. In the present study, we aimed to elucidate the role of EGF+61in glioma susceptibility and prognosis. Experimental Design:A case-control study involving197 glioma patients and 570 controlswas done. Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95% confidence intervals (95% CI). False-positive report probability was also assessed.The luciferase reporter gene assay was used to ascertain the functional consequences of this polymorphism. Results: Corroborating the univariate analysis, the multivariate model showed that the G allele conferred higher risks for gliomas (OR,1.32; 95% CI,1.04-1.67), glioblastomas (OR,1.47; 95% CI, 1.02-2.10), and oligodendrogliomas (OR,1.55; 95% CI,1.07-2.23).TheGG genotypeswere associatedwithincreased risk for gliomas (OR,1.71; 95%CI,1.07-2.73), glioblastomas (OR, 2.03; 95% CI, 1.02-4.05), and oligodendrogliomas (OR, 2.72; 95% CI, 1.18-6.28). In addition, the AG+GG genotypes were associated withhigher risk for gliomas (OR,1.52; 95% CI,1.03-2.23) and oligodendrogliomas (OR, 2.80; 95% CI,1.35-5.79). No significant associationwas observed between the EGF+61polymorphism and glioblastoma or oligodendroglioma patients’overall survival. The luciferase reporter gene assay exhibited a significant increased promoter activity for the G variant compared withthe referenceA allele. Conclusions: These findings support the role of the EGF+61polymorphism as a susceptibility factor for development of gliomas and show its implication on EGF promoter activity.