MOLECULAR-GENETIC MODELS FOR PROGNOSIS OF DEVELOPMENT OF TUMORS OF REPRODUCTIVE SYSTEM IN WOMEN WITH FAMILY HISTORY OF CANCER

Autor: O.V. Paliychuk, L.Z. Polishchuk, V.F. Chekhun, Z.I. Rossokha
Rok vydání: 2018
Předmět:
Zdroj: Experimental Oncology. 40:59-67
ISSN: 2312-8852
1812-9269
DOI: 10.31768/2312-8852.2018.40(1):59-67
Popis: Aim: To develop a prognostic molecular genetic model for assessing the risk of development of benign and malignant tumors of female reproductive organs (FRO) in patients from cancer-affected families. Patients and Methods: The work presents the data on a comprehensive clinical examination of 210 women (90 patients with FRO cancer with aggregation of tumor pathology in families, 65 patients with benign pathology of FRO from cancer-affected families, 55 women — control group of healthy women without family history of cancer). Clinical genealogical analysis, morphological examination of tumors and molecular genetic studies of genomic DNA from peripheral blood and tumors were carried out. Results: It was established that in the families of patients with benign and malignant pathology of FRO, malignant tumors associated with Lynch II syndrome are observed. Based on the analysis of detected ESR-1, CYP 2D6*4 and mutations in BRCA1/2 genes in cancer patients and in patients with benign pathology, molecular genetic models have been developed to assess the individual risk of development of benign and malignant tumors of FRO. It has been established that these molecular genetic models and combinations of gene mutations and gene polymorphisms (SNP) by the intergene interaction that was analyzed, were found to be reliable in assessing the risk of benign and malignant pathology of the mammary gland and ovary. Conclusions: The model, which included the polymorphic variants of the T397C(ESR1)/CYP 2D6*4 genes was of the best predictive accuracy for the evaluation of the risk of benign tumors of the FRO (71.68%) and the highest reliability (p < 0.001). At the same time, all identified models of intergene interaction in the development of malignant pathology of FRO were reliable, prognostically significant with high reproduction and almost identical accuracy (65.00–68.23%). The obtained results indicate a high informativeness of such molecular genetic indices as the polymorphism of ESR1 and CYP 2D6*4 genes and mutations in BRCA1/2 genes to assess the risk of benign or malignant tumors of FRO in families of patients with family history of cancer.
Databáze: OpenAIRE