Glushchenko N. Prognostication of genetic risk of development of malignant neoplasms under conditions of aggregation of tumor pathology in the pedigrees of patients with endometrial and ovarian cancer

The dissertation work theoretically substantiates and presents a new approach to solving the current problem in the field of oncology - an identification of people with a hereditary predisposition to cancer. On the basis of a comprehensive clinical and genealogical examination of patients with EC and OC and genetic and mathematical analysis, the contribution of genetic factors to the predisposition to the MN occurrence was determined. The expediency of medical and genetic counseling of healthy individuals and relatives of patients with cancer of different genesis has been demonstrated. Based on the algorithms for determining the contribution of the genetic determinant to the MN predisposition and the recurrent MN risk in the offspring, which are presented in the database of RE. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, in the module “Hereditary Cancer Syndromes”, it was found that the part of the genetic component in the predisposition to CFRS in the first degree relatives in the groups of patients with EC and OC was 53.2% and 58.2%, respectively, indicating the multifactorial nature of the pathology. In the families of patients with EC with the type of marriage “healthy parents” (N×N), the recurrent risk of cancer in the first child was 3.8%, and in the second - 6.0%. With the type of marriage “one or both parents are sick” (N×A and A×A), the risk increases up to 18.5% and 24.3%, respectively. In families of patients with OC with the type of marriage N×N, the risk of the MN developing in the first child was 2.3%, and in the second child - 4.0%, in contrast to the alternative family situation (N×A and A×A), where this index increased up to 24.1% and 38.0%, respectively. Highly informative risk factors for EC development on the background of atypical hyperplasia were identified: aggregation of CFRS and CGIT in the pedigrees of the I-II degree relatives (I = 0.93); duration of menopause of 1-4 years (I = 0.85); age of menarche 15 years and older (I = 0.71); no pregnancies (I = 0.55); the presence of uterine bleedings at menopause (I = 0.50); BMI of 36.0 kg/m2 and higher (I = 0.50). A web-oriented software product for predicting the MN occurrence under the conditions of aggregation of oncological diseases in the pedigrees “Cancer Genetic Risk” based on the objective approach to assessing the numerical equivalent of individual genetic risk of MN in the I and II degree relatives in order to form new strategies of cancer prevention has been developed. Criteria for assessing genetic risk have been determined: for persons younger than 50 years values ≥ 6.7% indicate a high risk of cancer development, while for persons 50 years and older values ≥ 7.3% indicate a high risk.