Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients

Gilmar Ferreira do Espírito Santo; Bianca Borsatto Galera; Elisabeth Carmen Duarte; Elisabeth Suchi Chen; Lenuce Azis; Amilcar Sabino Damazo; Gabriela Tognini Saba; Flávia de Sousa Gehrke; Ismael Dale Cotrim Guerreiro da Silva; Jaques Waisberg

doi:10.4251/wjgo.v9.i2.78

Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients

World J Gastrointest Oncol. 2017 Feb 15;9(2):78-86. doi: 10.4251/wjgo.v9.i2.78.

Affiliation

¹ 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.

Abstract

Aim: 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 the VEGF-A -1498C>T (rs833031) and -634G>C (rs2010963) polymorphisms. Genotyping was validated for VEGF-A -1498C>T polymorphism in 129 patients and for VEGF-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 the VEGF-A -1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A -1498C>T polymorphism and VEGF-A -634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-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 the VEGF-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 polymorphism VEGF-A -1498C>T and the genotype CC (HR = 3.76) of the polymorphism VEGF-A -634C>G acted as an independent prognostic factor for the risk of death in CRC patients.

Conclusion: The CT and CC genotypes of the VEGF-A -1498C>T and the CC genotype of the VEGF-A -634C>G polymorphisms are prognostic factors of survival in Brazilians patients with sporadic colorectal carcinoma.

Keywords: Colorectal cancer; Colorectal surgery; Genetic polymorphisms; Genetic variation; Vascular endothelial growth factor-A.