Association between functional EGF+61 polymorphism and glioma risk.
OBJECTIVE
Epidermal growth factor (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+61 in glioma susceptibility and prognosis.


METHODS
A case-control study involving 197 glioma patients and 570 controls was 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). The GG genotypes were associated with increased 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 with higher 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 association was observed between the EGF+61 polymorphism and glioblastoma or oligodendroglioma patients' overall survival. The luciferase reporter gene assay exhibited a significant increased promoter activity for the G variant compared with the reference A allele.


CONCLUSIONS
These findings support the role of the EGF+61 polymorphism as a susceptibility factor for development of gliomas and show its implication on EGF promoter activity.
Costa
Bruno Marques
BM
Life and Health Sciences Research Institute (ICVS), School of Health Sciences and Department of Production and Systems Engineering, University of Minho, Braga, Portugal.
Ferreira
Paulo
P
Costa
Sandra
S
Canedo
Paulo
P
Oliveira
Pedro
P
Silva
Ana
A
Pardal
Fernando
F
Suriano
Gianpaolo
G
Machado
José Carlos
JC
Lopes
José Manuel
JM
Reis
Rui Manuel
RM
D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004815:Epidermal Growth Factor / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012306:Risk
D004815:Epidermal Growth Factor