title: Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients.
abstract: OBJECTIVE
  To investigate the associations of the genetic polymorphisms of vascular endothelial growth factor A (VEGF-A) -1498C>T and -634G>C, with the survival of patients with colorectal cancer (CRC).
  
  
  METHODS
  A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction (PCR) in real-time. The real-time PCR technique was used to identify theVEGF-A-1498C>T (rs833031) and -634G>C (rs2010963) polymorphisms. Genotyping was validated forVEGF-A-1498C>T polymorphism in 129 patients and forVEGF-A-634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method.
  
  
  RESULTS
  In the univariate analysis there was a significant association (OR = 0.32;P= 0.048) between genotype CC of theVEGF-A-1498C>T polymorphism and the presence of CRC liver metastasis. There was no association betweenVEGF-A-1498C>T polymorphism andVEGF-A-634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of theVEGF-A-1498C>T polymorphism was significantly correlated with the 5-year survival (P= 0.032), but not significant difference (P= 0.27) was obtained with theVEGF-A-634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT (HR = 2.79) and CC (HR = 4.67) of the polymorphismVEGF-A-1498C>T and the genotype CC (HR = 3.76) of the polymorphismVEGF-A-634C>G acted as an independent prognostic factor for the risk of death in CRC patients.
  
  
  CONCLUSIONS
  The CT and CC genotypes of theVEGF-A-1498C>T and the CC genotype of theVEGF-A-634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.
authors.affiliation: Gilmar Ferreira do Espírito Santo, Gabriela Tognini Saba, Jaques Waisberg, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, São Paulo 04024-002, Brazil.
authors.forename: Gilmar Ferreira
authors.initials: GF
authors.lastname: do Espírito Santo
authors.affiliation: Gilmar Ferreira do Espírito Santo, Gabriela Tognini Saba, Jaques Waisberg, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, São Paulo 04024-002, Brazil.
authors.forename: Bianca Borsatto
authors.initials: BB
authors.lastname: Galera
authors.affiliation: Gilmar Ferreira do Espírito Santo, Gabriela Tognini Saba, Jaques Waisberg, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, São Paulo 04024-002, Brazil.
authors.forename: Elisabeth Carmen
authors.initials: EC
authors.lastname: Duarte
authors.affiliation: Gilmar Ferreira do Espírito Santo, Gabriela Tognini Saba, Jaques Waisberg, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, São Paulo 04024-002, Brazil.
authors.forename: Elisabeth Suchi
authors.initials: ES
authors.lastname: Chen
authors.affiliation: Gilmar Ferreira do Espírito Santo, Gabriela Tognini Saba, Jaques Waisberg, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, São Paulo 04024-002, Brazil.
authors.forename: Lenuce
authors.initials: L
authors.lastname: Azis
authors.affiliation: Gilmar Ferreira do Espírito Santo, Gabriela Tognini Saba, Jaques Waisberg, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, São Paulo 04024-002, Brazil.
authors.forename: Amilcar Sabino
authors.initials: AS
authors.lastname: Damazo
authors.affiliation: Gilmar Ferreira do Espírito Santo, Gabriela Tognini Saba, Jaques Waisberg, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, São Paulo 04024-002, Brazil.
authors.forename: Gabriela Tognini
authors.initials: GT
authors.lastname: Saba
authors.affiliation: Gilmar Ferreira do Espírito Santo, Gabriela Tognini Saba, Jaques Waisberg, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, São Paulo 04024-002, Brazil.
authors.forename: Flávia
authors.initials: F
authors.lastname: de Sousa Gehrke
authors.affiliation: Gilmar Ferreira do Espírito Santo, Gabriela Tognini Saba, Jaques Waisberg, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, São Paulo 04024-002, Brazil.
authors.forename: Ismael Dale Cotrim
authors.initials: ID
authors.lastname: Guerreiro da Silva
authors.affiliation: Gilmar Ferreira do Espírito Santo, Gabriela Tognini Saba, Jaques Waisberg, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, São Paulo 04024-002, Brazil.
authors.forename: Jaques
authors.initials: J
authors.lastname: Waisberg
keywords: Colorectal cancer; Colorectal surgery; Genetic polymorphisms; Genetic variation; Vascular endothelial growth factor-A