title: Association between functional EGF+61 polymorphism and glioma risk.
abstract: 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.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences and Department of Production and Systems Engineering, University of Minho, Braga, Portugal.
authors.forename: Bruno Marques
authors.initials: BM
authors.lastname: Costa
authors.forename: Paulo
authors.initials: P
authors.lastname: Ferreira
authors.forename: Sandra
authors.initials: S
authors.lastname: Costa
authors.forename: Paulo
authors.initials: P
authors.lastname: Canedo
authors.forename: Pedro
authors.initials: P
authors.lastname: Oliveira
authors.forename: Ana
authors.initials: A
authors.lastname: Silva
authors.forename: Fernando
authors.initials: F
authors.lastname: Pardal
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Suriano
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Machado
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Lopes
authors.forename: Rui Manuel
authors.initials: RM
authors.lastname: Reis
mesh_terms: 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
chemical_list: D004815:Epidermal Growth Factor