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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Feb 15, 2017; 9(2): 78-86
Published online Feb 15, 2017. doi: 10.4251/wjgo.v9.i2.78
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
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
Bianca Borsatto Galera, Lenuce Azis, Amilcar Sabino Damazo, Genetic Laboratory Basics Health Sciences Department, Medical School of Federal University of Mato Grosso, Cuiabá 78060-900, Brazil
Elisabeth Carmen Duarte, Tropical Medicine Division, Medical School of Brasilia University, Campus Darcy Ribeiro University, Brasília 70904-970, Brazil
Elisabeth Suchi Chen, Laboratory of Genetics of Morphology and Genetics Department, Federal University of São Paulo, São Paulo 04023-900, Brazil
Flávia de Sousa Gehrke, Laboratory of Clinical Analysis, ABC Medical School, avenida Príncipe de Gales, Santo André 09060-650, Brazil
Ismael Dale Cotrim Guerreiro da Silva, Laboratory of Molecular Gynecology, Department of Gynecology, Federal University of São Paulo, rua Pedro de Toledo, São Paulo 04039-032, Brazil
Author contributions: do Espírito Santo GF, Galera BB and Waisberg J participated in the design of the study, statistical analysis and the manuscript preparation; Chen ES, Azis L and Damazo AS participated in the sample collection and analyzed the data from the real-time PCR assays; Duarte EC performed the statistical analyses; do Espírito Santo GF, Galera BB, Saba GT, de Sousa Gehrke F and Guerreiro da Silva IDC participated in the manuscript preparation; all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Research Ethic Committee of UNIC (University of Cuiabá) and in the Research Ethic Committee of Federal University of São Paulo.
Informed consent statement: All study participants, or their legal guardian, provided written consent prior to study enrollment.
Conflict-of-interest statement: The authors of this manuscript having no conflicts of interest to disclose.
Data sharing statement: There is no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jaques Waisberg, MD, PhD, FACS, Department of Surgery - Escola Paulista de Medicina, Federal University of São Paulo, Rua Napoleão de Barros, 715, Vila Clementino, São Paulo 04024-002, Brazil.
jaqueswaisberg@uol.com.br
Telephone: +55-11-982560018 Fax: +55-11-44368739
Received: June 24, 2016
Peer-review started: June 24, 2016
First decision: August 18, 2016
Revised: September 18, 2016
Accepted: December 13, 2016
Article in press: December 14, 2016
Published online: February 15, 2017
Processing time: 235 Days and 14.8 Hours
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.
Core tip: Vascular endothelial growth factor A (VEGF-A) affects the tumor biological behavior and phenotype. An applied research with relevant achievement that will possibly be favored by such information is the pharmacogenetics impact of VEGF-A polymorphisms. VEGF-A is a significant goal in the anticancer therapy and results about VEGF-A polymorphisms may enhance the targeted therapies. This approach will be of great help to the suitability of individual therapies and improve the quality of post operative treatment. Moreover, since polymorphisms often show a discrepancy between ethnic groups, more studies are also warranted to clarify the association between the VEGF-A polymorphisms and the CRC in diverse ethnic populations.
