Background: Epigenetic regulation of genes plays an important role in the development of ovarian cancer. One of these mechanisms is DNA methylation of tumor suppressor genes and oncogenes. A detailed study of methylation can serve as an important step towards improving the methods of early screening for OC. The aim of the study: Based on the study of modern literature data, to consider the role of DNA methylation in the pathogenesis of ovarian cancer and evaluate its contribution to the development of this disease. Materials and methods: Literature data were analyzed using the following keywords: DNA methylation, ovarian cancer, epigenetic regulation, epidemiology of ovarian cancer. Results: According to the literature data, hypermethylation of promoters of suppressor genes or, conversely, hypomethylation of oncogenes is noted in oncological diseases. Thus, it has been established that hypermethylation of the promoters of the OPCML, PAX1, CDH1, HOXA9, HIC1, MLH1 genes is often observed in ovarian cancer. Methylation of the HIST1H2BB, MAGI2, HOXA10 and HOXA11, LAMA3, ESR1, TNF, MUC1 and FOXO1 genes has an important diagnostic and/or prognostic value. The methylation of miRNA genes plays a special role in the progression of ovarian cancer. Conclusion: In contrast to genetic changes, DNA methylation is a reversible process, which is very promising for the development of new therapeutic approaches and for early diagnosis of the disease, where hypermethylation of gene promoters can serve as biomarkers. Numerous studies support the important role of methylation tumor suppressor genes and various microRNAs in oncogenesis, and predisposes to the development of a field of research aimed at deciphering the human epigenome. Understanding the mechanisms of epigenetic regulation of the development and course of cancer will contribute to the development of new diagnostic and prognostic methods and approaches for cancer treatment.
Background: Pregnancy complications have a high prevalence and important medical and social implications. Genetic factors are involved in their development. The aim of the study: To study the characteristics of interlocus interactions in the formation of isolated and combined pregnancy complications. Materials and methods: The sample for the study consisted of 786 pregnant women, including 462 women were with various pregnancy complications (isolated preeclampsia (PE) (n=190); 2) isolated fetal growth retardation (FGR) (n=196); 3) a combination of PE and FGR (n=76)) and 324 women with a physiological course of pregnancy. Genotyping was performed for 13 polymorphic loci of growth factor genes and their receptors (rs4444903 EGF, rs833061 VEGFA, rs2981582 FGFR2, rs6214 IGF1, rs1800469 TGFß1), estrogen and progesterone receptor genes (rs2234693 ESR1, rs9340799 ESR1, rs3798577 ESR1, rs484389 PGR, rs1042838 PGR) and hereditary thrombophilia genes (rs1126643 ITGA2, rs5918 ITGB3 and rs5985 F13A1). The interaction of polymorphic loci associated with the studied pregnancy complications, visualization and determination of the nature (synergism, independent effect, antagonism) and strength (proportion of contribution to the entropy of the trait) of these interactions were studied using MB-MDR and MDR methods. Results: The risk of developing isolated FGR is determined by three models of interlocus interactions of 5 polymorphisms: rs4444903 EGF, rs6214 IGF1, rs2234693 ESR1, rs484389 PGR and rs5985 F13A1 with the most pronounced effects of the polymorphic locus rs6214 IGF1. Susceptibility to isolated PE is determined by the interlocus interactions of five loci: rs4444903 EGF, rs833061 VEGFA, rs2981582 FGFR2, rs2234693 ESR1, rs9340799 ESR1, in which the two-locus interaction rs9340799 ESR1xrs2234693 ESR1 plays a key role (it is part of all 3 models). The formation of a combination of FGR and PE is associated with two models of intergenic interactions of 4 polymorphisms: rs2234693 ESR1, rs9340799 ESR1, rs484389 PGR, rs5918 ITGB3. Three high-risk genotype combinations of genotypes showed the highest level of statistical significance of associations (p<0.005) with pregnancy complications: TT-rs2234693 ESR1xGA-rs6214 IGF1 – isolated FGR (β = 1.86, p=0.003); AA-rs9340799 ESR1xTT-rs2234693 ESR1 – isolated PE (β = 2.45, p=0.0009) and the combination of PE and FGR (β = 2.38, p=0.002). Conclusion: The risk of pregnancy complications is largely determined by the genetic combinatorics of the three polymorphic loci rs2234693 ESR1, rs9340799 ESR1, rs6214 IGF1.
