Abstract
Vascular endothelial growth factor (VEGF) is one of the most important and specific factors affecting angiogenesis in tumor development. VEGFR2 is a receptor encoded by the KDR gene. VEGF and VEGFR2 transmit a signal to intracellular tyrosine kinase cascades. Polymorphic variants of the VEGF and KDR genes significantly influence the expression levels of the endothelial growth factor and its receptor, which leads to a change in the activation of angiogenesis in oncopathological processes. In this study, the relationship between the polymorphic variants rs2010963, rs699947 and rs3025039 of the VEGF gene and rs1870377 and rs2071559 of the KDR gene was analyzed with the development of a specific histological type of non-small cell lung cancer and its clinical and morphological characteristics. It was established that the development of squamous cell carcinoma is associated with -634CC genotype of the VEGF gene and the genotypes containing -2578A allele of the VEGF gene reduce the likelihood of this cancer type development. The development of adenocarcinoma is associated with +936CC VEGF/1719TT KDR and +936CT VEGF/1719TT KDR combinations. In women with non-small cell lung cancer, -634GC genotype of the VEGF gene is associated with a greater degree of the primary lesion spread. Genotype -2578СС of the VEGF gene is associated with a higher degree of the primary tumor spread in the general group of patients and with regional metastases in women. Haplotypes -634G/-2578C/+936C are risky for the occurrence of metastases in regional lymph nodes in women.
Highlights
Lung cancer is one of the most common malignant neoplasms and the leading causes of death from cancer in men
It was established that the development of squamous cell carcinoma is associated with −634CC genotype of the Vascular endothelial growth factor (VEGF) gene and the genotypes containing −2578A allele of the VEGF gene reduce the likelihood of this cancer type development
Genotype −2578СС of the VEGF gene is associated with a higher degree of the primary tumor spread in the general group of patients and with regional metastases in women
Summary
Lung cancer is one of the most common malignant neoplasms and the leading causes of death from cancer in men. The key process in the NSCLC development is angiogenesis. One of the most important and specific factors affecting angiogenesis in tumor development is vascular endothelial growth factor VEGF [1] [2]. The main receptor through which VEGF transmits a signal to intracellular tyrosine kinase cascades is the VEGFR2 receptor encoded by the KDR gene [3] [4]. The VEGF gene triggers the activation of the protease cascade involved in the degradation of extracellular matrix, suppressing apoptosis, stimulates the endothelial cells survival, increases vascular permeability, inhibits the dendritic cells differentiation as well as activates tissue factors and monocytes migration [6]. Polymorphic variants of the VEGF and KDR genes significantly influence the expression levels of the endothelial growth factor and its receptor, which leads to a change in the activation of angiogenesis in oncopathological processes. The studies of molecular genetic disorders of these genes that will allow predicting the development and progress of this disease are of great importance
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