GENETIC TESTING OF CONSTITUTIVE SENSITIVITY TO METFORMIN IN CANCER PATIENTS WITH AND WITHOUT DIABETES
Metformin (MF) belongs to the most popular andidiabetic medicines and is considered to possess a selective antineoplastic action. This selectivity at least partly may be explained by the certain features of MF pharmacogenetics. More than 150 postmenopausal females divided into 4 groups (cancer +diabetes type 2 (DM2); cancer without DM2; DM2 without cancer, and healthy) were studied. Genetic polymorphisms of the two groups of genes — entitled on the basis of the relation to potential MF effect as a ‘standard’ (S) or ‘associated’ (A) — were under investigation. Among S-markers a most informative in regard of MF response prediction appeared to be polymorphisms of OCT1-R61C organic cation transporter protein 1 gene and serin/threonine kinase STK11. In the group of A-polymorphisms the GC genotype of oxidized lipoprotein receptor OLR1_G501C demonstrated tendency to the combination with ‘MF-positive’ variant of OCT1_R61C. The carriers of the latter were characterized with insulin resistance while carriers of STK11 variants — with lower blood estradiol level. Postmenopausal diabetics with as well as without cancer, differ in genetic markers of potential response to metformin less than they differ from cancer patients without DM2.