PROMOTER POLYMORPHISMS OF GENES ENCODING TUMOR NECROSIS FACTOR AND INTERLEUKIN-1 IN BREAST CANCER PATIENTS

Search for molecular genetic markers of risk and prognosis of breast cancer is an important prospective of modern research. Many molecular mechanisms are involved in pathogenesis of breast cancer and define a wide range of possible candidate genes. The genes of pro-inflammatory cytokine receptors, such as tumor necrosis factor and interleukin-1, are also among potential candidate genes. Numerous functional allelic variants of these genes have been shown which are associated with changed expression of membranebound and soluble forms of the receptors. In addition, they are expressed both on immunе cells and epithelial and endothelial cells. They regulate functional status of the cells, synthesis and activities of enzymes controlling extracellular matrix and angiogenesis factors. These functions of tumor necrosis factor and interleukin-1 receptor proteins may contribute to pathogenesis of tumor growth. The aim of present study was to compare frequency of functional allelic variants of genes encoding TNF and IL-1 receptors in breast cancer patients and healthy women. We performed genotyping of distinct SNPs (rs4149569 TNFRSF1A, rs590368 TNFRSF1B, rs2234650 IL1RI, and rs4141134 IL1R2) that previously were shown to be associated with expression of TNF and IL-1 receptors on immune cells. Comparative analysis of the genotype frequencies in the samples under study showed a significantly reduced frequency of CC homozygotes for rs590368 polymorphism (TNFRSF1B gene), and increased ratio of CT heterozygotes for rs2234650 polymorphism (IL1R1 gene) among breast cancer patients. Hence, some gene polymorphisms associated with altered expression levels of TNF and IL-1 receptors on immune cells may represent a factor which may determine involvement of proinflammatory cytokines into pathogenesis of breast cancer.

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