GENETIC DETERMINANTS OF HYPERPLASTIC DISEASES OF THE ENDOMETRIUM AND MAMMARY GLANDS

Genetic predisposition constitutes a well-established etiological factor in the pathogenesis of proliferative diseases of the mammary gland and uterus. Empirical evidence from cytogenetic and epidemiological studies substantiates a heritable component in the development of uterine hyperplastic processes (UHPP). Objective. The aim of our study was to investigate the significance of rs1138272 polymorphisms in the GSTP1 (Ala/Val) gene and rs5918 polymorphisms in the ITGB3 (T/C) gene in the mechanisms underlying the development of hyperplastic processes of the endometrium and/or myometrium, concomitant with benign breast dysplasia in perimenopausal women. Methods. A total of 82 patients with a confirmed diagnosis of endometrial and/or myometrial hyperplastic processes were enrolled. In addition to standard diagnostic protocols for uterine hyperplastic conditions, all study participants underwent genetic analysis. The study cohort was divided into a main group (n=50) of patients with UHPP and co-existing benign breast dysplasia, and a comparison group (n=32) of patients with UHPP without breast pathology. The control group consisted of 80 clinically healthy women. The principles of bioethics, approved by the Scientific Council of Samarkand State Medical University, are preserved and upheld in full compliance. To variationally estimate the frequency of genotypes of the studied rs 5918 polymorphism in the ITGB3 gene (T/C), the agreement was analyzed between the expected (Hexp) and observed (Hobs) frequencies of their distribution in the groups of patients with UHPP and controls, in accordance with the Hardy-Weinberg equilibrium (PXB, p>0.05). The work was carried out within the framework of the scientific project No. 012000260 "Development of promising technologies for the prevention, diagnostics, and treatment of infectious and non-infectious diseases of the human body that have social significance" in accordance with the research plan of Samarkand State Medical University. Results. In the main group, the expected (Hexp) and observed (Hobs) frequencies of the T/T, T/C, and C/C genotypes for rs5918 in the ITGB3 gene (T/C) were 0.85 and 0.86 (χ²=0.00), 0.15 and 0.14 (χ²=0.07), and 0.00 and 0.01 (χ²=0.44), respectively, with no statistically significant differences (p=0.45). In the control group, the frequencies were: 0.83 and 0.83 (χ²=0.01), 0.18 and 0.16 (χ²=0.12), and 0.00 and 0.10 (χ²=0.61), also without significant differences (p=0.37). Discussion. The findings suggest that the rs5918 polymorphism in the ITGB3 gene is not a principal driver mutation in the pathogenesis of hyperplastic diseases of the uterus and mammary glands. Furthermore, within the subgroup of patients with UHPP, no association was identified between this polymorphism and concomitant breast pathology. However, among patients who presented with abnormal uterine bleeding (AUB), the heterozygous T/C genotype was significantly more common. Conclusion. A solitary genetic polymorphism may exert a negligible effect on complex physiological systems; however, the aggregate effect of alterations in multiple genes can significantly disrupt systemic homeostasis and precipitate pathological states. Consequently, the investigation of genetic susceptibility to multifactorial diseases necessitates the evaluation of polygenic models or the analysis of multiple polymorphisms within pertinent gene pathways.