title: Impact of EGFR genetic variants on glioma risk and patient outcome.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, -216G/T and -191C/A, and a polymorphic (CA)(n) microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis.
  
  
  METHODS
  We conducted a case-control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed.
  
  
  RESULTS
  None of the EGFR -216G/T variants was significantly associated with glioma risk. The -191C/A genotype was associated with higher risk for glioma when the (CA)(n) alleles were classified as short for ≤16 or ≤17 repeats. Independently of the (CA)(n) repeat cutoff point used, shorter (CA)(n) repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA)(n) cutoff points, only -191C/A genotype was consistently associated with improved survival of patients with glioblastoma.
  
  
  CONCLUSIONS
  Our findings implicate EGFR -191C/A and the (CA)(n) repeat polymorphisms as risk factors for gliomas, and suggest -191C/A as a prognostic marker in glioblastoma.
  
  
  CONCLUSIONS
  Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal.
authors.forename: Bruno Marques
authors.initials: BM
authors.lastname: Costa
authors.forename: Marta
authors.initials: M
authors.lastname: Viana-Pereira
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernandes
authors.forename: Sandra
authors.initials: S
authors.lastname: Costa
authors.forename: Paulo
authors.initials: P
authors.lastname: Linhares
authors.forename: Rui
authors.initials: R
authors.lastname: Vaz
authors.forename: Céline
authors.initials: C
authors.lastname: Pinheiro
authors.forename: Jorge
authors.initials: J
authors.lastname: Lima
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.forename: Ana
authors.initials: A
authors.lastname: Silva
authors.forename: Fernando
authors.initials: F
authors.lastname: Pardal
authors.forename: Júlia
authors.initials: J
authors.lastname: Amorim
authors.forename: Rui
authors.initials: R
authors.lastname: Nabiço
authors.forename: Rui
authors.initials: R
authors.lastname: Almeida
authors.forename: Carlos
authors.initials: C
authors.lastname: Alegria
authors.forename: Manuel Melo
authors.initials: MM
authors.lastname: Pires
authors.forename: Célia
authors.initials: C
authors.lastname: Pinheiro
authors.forename: Ernesto
authors.initials: E
authors.lastname: Carvalho
authors.forename: Pedro
authors.initials: P
authors.lastname: Oliveira
authors.forename: José M
authors.initials: JM
authors.lastname: Lopes
authors.forename: Rui M
authors.initials: RM
authors.lastname: Reis
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005838:Genotype; D005910:Glioma / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012307:Risk Factors
chemical_list: D066246:ErbB Receptors