The Role of Polymorphic Variants of Several Genes of Matrix Metalloproteinases and Their Tissue Inhibitors in the Development of Gastric Cancer

The main function of matrix metalloproteinases is the degradation of the extracellular matrix and participation in signal transduction. In addition, it is known that they are involved in all stages of the progression of the tumor process. The activity of metalloproteinases can be regulated by interactions with specific inhibitors of matrix metalloproteinases, so the latter are also able to participate in tumor growth. The genes of matrix metalloproteinases and their inhibitors, as well as many other genes, are characterized by polymorphism. We have analyzed the frequency distribution of the alleles and genotypes of the polymorphic loci rs1799750 and rs494379 of the MMP1 gene, rs2285053 of the MMP2 gene, rs3025058 of the MMP3 gene, rs3918242 and rs17576 of the MMP9 gene, rs2276109 of the MMP12 gene, rs8179090 of the TIMP2 gene, and rs9619311 of the TIMP3 gene in 314 patients with gastric cancer, as well as in 339 unrelated healthy individuals from the Republic of Bashkortostan. It was shown that the markers of the increased risk of developing gastric cancer are the genotypes rs1799750*1G/2G of the MMP1 gene and rs2276109*A/A of the MMP12 gene for Tatars and the genotype rs9619311*T/T of the TIMP3 gene for Russians. The association of the rs494379*G allele of the MMP1 gene and increased risk of developing malignant tumors of the stomach were reported in men. Using the APSampler algorithm, we identified combinations of alleles/genotypes associated with an increased and a reduced risk of developing gastric oncopathologies. The data obtained confirm the influence of the studied polymorphic variants of the genes of matrix metalloproteinases and their tissue inhibitors on the risk of developing gastric cancer and are important for understanding the genetic structure of the studied pathology.