Romak R. Improving the diagnosis and prognosis of proliferative breast diseases by assessing the genes DKK4 and GSR methylation status

The thesis is devoted to the improvement of diagnosis and prognosis of proliferative breast diseases by assessing the genes DKK4 and GSR methyla-tion status. It was determined that the main risk factors for breast tumors development is the presence of gynecological diseases and endocrine disorders , late menarche , age over 35. Burdened hereditary history of breast pathology takes place in 78.0% of patients, cases of breast cancer in first-degree relatives were found in 34.0% of patients. The rate of polymorphisms rs3763511 of gene DKK4 and rs8190924 of gene GSR among women with benign hyperplasia and breast cancer do not dif-fer . While assessing the distribution of different genotypes in the selective aggregate it was established that in women with breast cancer homozygous and heterozygous genotypes distribution for the in-vestigated polymorphisms did not correspond to Hardy-Weinberg equation, both women with benign breast dysplasia and women of control group had steady state genotypes distribution. The level of gene DKK4 methylation in patients with proliferative breast diseases was proved lower than in patients with breast cancer, when the intensity of methylation was 62.0%. GSR gene methylation activity in patients with breast cancer is almost three times higher than in healthy women. With values of GSR gene methylation activity in patients with breast tumors lower than 17.8% the probability of malignant tumors is low. GSR gene methylation activity over 24.9% is typical for breast cancer. There was developed and implemented an algorithm for early diagnosis and prognosis of breast cancer using epigenetic research.