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

Abstract

AIMTo 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).METHODSA 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.RESULTSIn 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.CONCLUSIONThe 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.

Sexual Dimorphism in Colon Cancer

“…Hypoxia (≤3% oxygen) and anoxia (≤0.3% oxygen) are potent drivers of cancer cell proliferation, angiogenesis, metastatic potential and resistance to chemo-and radio-therapy (108). The induction and activation of the hypoxia-inducible transcription factor HIF1A and the HIF target of vascular endothelial growth factor alpha (VEGFA) are separately associated with poor CRC clinical outcome (109,110).…”

“…Hypoxia (≤3% oxygen) and anoxia (≤0.3% oxygen) are potent drivers of cancer cell proliferation, angiogenesis, metastatic potential and resistance to chemo- and radio-therapy ( 108 ). The induction and activation of the hypoxia-inducible transcription factor HIF1A and the HIF target of vascular endothelial growth factor alpha (VEGFA) are separately associated with poor CRC clinical outcome ( 109 , 110 ). Functional cross-talk between GPER activation and EGF signalling has been demonstrated in CRC ER-negative cell lines and modulates the potential for CRC cell proliferation and migration ( 111 ).…”

Circulating vascular endothelial growth factor and cancer risk: A bidirectional mendelian randomization

“…Several previous observational studies have found that polymorphisms in VEGF may predispose patients to colorectal cancer susceptibility ( Kim et al, 2008 ; Zhao et al, 2012 ; Jang et al, 2013 ; Espírito Santo et al, 2017 ; Yang et al, 2017 ). Jang et al studied 882 participants in the Korean population, including 390 colorectal patients and 492 controls.…”

Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging

“…• Another prospective study of CRC patients aimed to investigate the correlation between genetic polymorphism of VEGF-A with survival using the DNA extracted from peripheral blood. In a 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 [70].…”