title: Analysis of EGF+61A>G polymorphism and EGF serum levels in Brazilian glioma patients treated with perillyl alcohol-based therapy.
abstract: OBJECTIVE
  Malignant gliomas are associated with alteration in EGF/EGFR signaling. Functional EGF+61A>G polymorphism is implicated with risk, recurrence, and progression of glioma. This study aimed to establish a putative association of EGF+61A>G with risk of glioma development, production of angiogenic growth factor EGF, and the response to perillyl alcohol administered by intranasal route.
  
  
  METHODS
  The study included 83 patients with recurrent glioma enrolled in Phase I/II trial for intranasal perillyl alcohol therapy and subjects without cancer (n = 196) as control group. DNA was extracted from blood samples, EGF genotype performed with PCR-RFLP assay, and EGF circulating levels by enzyme immunoassay. Adequate statistical tests were performed to verify associations between polymorphism and glioma risk, and genotype correlation with EGF circulating levels. The log-rank test was also used to evaluate differences on patient survival.
  
  
  RESULTS
  Patients with primary glioblastoma had high frequency of AA genotype (p = 0.037) and A allele (p = 0.037). Increased EGF circulating levels were observed in glioma patients with AA (p = 0.042), AG (p = 0.006), and AA + AG (p = 0.008) genotypes compared with GG. Patients with GG genotype showed increased but not significant (p > 0.05) survival rate, and EGF levels lower than 250 pg/mL was consistently (p = 0.0374) associated with increased survival.
  
  
  CONCLUSIONS
  Presence of EGF+61A>G polymorphism in Brazilian subjects was associated with glioma risk and increased circulating EGF levels. Better response to perillyl alcohol-based therapy was observed in a group of adult Brazilian subjects with lower EGF levels.
authors.affiliation: Department of Neurobiology, Institute of Biology, Fluminense Federal University, Niterói, RJ, Brazil.
authors.forename: Francisco das Chagas Abreu
authors.initials: Fd
authors.lastname: da Silveira
authors.forename: Bruno de Almeida
authors.initials: Bde A
authors.lastname: Lopes
authors.forename: Clovis Orlando
authors.initials: CO
authors.lastname: da Fonseca
authors.forename: Thereza
authors.initials: T
authors.lastname: Quirico-Santos
authors.forename: Izabel Christina Nunes
authors.initials: IC
authors.lastname: de Palmer Paixão
authors.forename: Lidia Maria da Fonte
authors.initials: LM
authors.lastname: de Amorim
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001932:Brain Neoplasms / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D001938:Brazil; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004815:Epidermal Growth Factor / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005910:Glioma / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D039821:Monoterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D039821:Monoterpenes; C032208:perillyl alcohol; D004815:Epidermal Growth Factor