The observed aberrant methylation frequencies of the RASSF1A and APC gene promoters indicate that an accumulation of epigenetic events at these specific TSG promoters may be associated with the malignant transformation of benign cystadenomas and LMP tumours to carcinomas.
Vascular endothelial growth factor (VEGF) plays an important role in the development of Breast Cancer. The aim of this study was to investigate the association of polymorphisms in the VEGF gene on prognosis of Breast Cancer patients. This study comprised 200 patients with histologically confirmed cases of Breast cancer and 200 controls. Genotyping of the VEGF gene polymorphisms at +405G>C,-1154G>A, were performed by PCR-RFLP analysis. Preoperative plasma VEGF levels were determined by ELISA. Amongst both cases and controls, the genotypic distribution of the individual SNPs were all in Hardy-Weinberg equilibrium. Mean VEGF level was significantly elevated in cases compared to controls (t = 8.248; P < 0.001). No significant association was found between +405G>C,-1154G>A VEGF polymorphism and Breast Cancer. Logistic regression analysis revealed that 405GG & 1154GG were associated with higher levels of VEGF.
Objective: Angiogenesis is necessary for tumor growth, invasion, and metastasis. A key mediator in neoangiogenesis is vascular endothelial growth factor (VEGF). DNA sequence variations in the VEGF gene may lead to altered VEGFexpression and/or activity, thereby causing interindividual differences in the susceptibility to breast cancer via their actions on the pathways of tumor angiogenesis. This study was undertaken to study the prevalence of VEGF +405G>C polymorphisms in Indian population and its association with plasma VEGF levels. Methods: The study comprised 200 patients with histologically confirmed patients of Breast cancer and 200 normal healthy females as controls. Polymerase chain reaction and restriction fragment length polymorphism were used for genotyping of VEGF +405G>C polymorphism. Preoperative plasma VEGF levels were determined by enzyme-linked immunosorbant assay (ELISA) in patients and controls. Results: Amongst both patients and controls, the genotypic distribution of the VEGF +405G>C polymorphism were in consistent with Hardy-Weinberg equilibrium. Mean VEGF level was significantly elevated in patients compared to controls (t=8.248; P<0.001). Plasma VEGF levels correlated significantly with clinical stage of the disease (P=0.035). Significantly elevated levels of VEGF(P<0.001) were seen in patients with the '+405GG&GC' genotype when compared with the respective control group. Conclusion: Since all the three genotype +405(GG,GC&CC) were showing an increased plasma VEGF levels, our study did not prove that mutant CC genotype is associated with higher VEGF expression. But we have found that plasma VEGF levels were significantly correlated with clinical stage of the disease. This may help to differentiate the subgroups of patients with poor prognosis who may benefit from validated anti-VEGF treatments.
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