Gastric cancer (GC) is one of the most common cancer types in the world with a high mortality rate. Hereditary predisposition for GC is not fully elucidated so far. The aim of this study was identification of possible new candidate genes, associated with the increased risk of gastric cancer development. Whole exome sequencing (WES) was performed on 18 DNA samples from adenocarcinoma specimens and non-tumor-bearing healthy stomach tissue from the same patient. Three pathogenic variants were identified: c.1320+1G>A in the CDH1 gene and c.27_28insCCCAGCCCCAGCTACCA (p.Ala9fs) of the VEGFA gene were found only in the tumor tissue, whereas c.G1874C (p.Cys625Ser) in the FANCA gene was found in both the tumor and normal tissue. These changes were found only in patients with diffuse gastric cancer and were absent in the DNA of healthy donors.

Gastric cancer (GC) is one of the most serious diseases, occupying a leading position among the causes of death from malignant neoplasms in the world. The Republic of Bashkortostan (RB) also has high rates of morbidity and mortality due to malignant neoplasms of the stomach. One of the main genes that determine a high risk of predisposition to this pathology is the CDH1 gene. The aim of the study: Search for changes in the nucleotide sequence in the CDH1 gene in patients with gastric cancer from the Republic of Bashkortostan. Materials and methods: The material for the study was DNA samples of gastric cancer patients and healthy donors living in the RB. Genomic DNA was isolated from peripheral blood lymphocytes by phenol-chloroform extraction. Amplifica-tion was performed using specific primers flanking the studied exon. The study of exons for the presence of changes in the nucleotide sequence was carried out using the SSCP and HRM methods. To verify molecular genetic changes, the Sanger sequencing method was used. Results: The genetic variant rs35741240 (c.1680G>C, p.Thr560=) was found in the 11th exon of the CDH1 gene. Four patients (1.33%) were found to be heterozygous C allele carriers among patients; the incidence of GC genotype among healthy individuals was 0.67% (2 patients). A rare polymorphic locus rs33969373 (c.1896C>T, p.His571=) was also found in the 12th exon of the CDH1 gene. The vari-ant was also detected in the heterozygous state, the frequency of the CT genotype in the group of patients was 1.00% (3 patients), among the control – 0.33% (1 patients). In exon 14 of the CDH1 gene, a synonymous polymorphic locus rs33964119 (c.2253C>T, p.Asn751=) was found. It was shown that this variant in the heterozygous state occurs in 24 patients (8.00%), and among healthy individuals the frequency of the CT genotype was 5.33% (16 patients). Pairwise comparison of the frequencies of alleles and genotypes of the identified loci between the groups of patients and con-trols revealed no statistically significant differences (p>0.05). Conclusion: As a result of the study, we found previously known changes in the nucleotide sequence in exons 11, 12 and 14 of the CDH1 gene (rs35741240, rs33969373 and rs33964119). None of the identified changes is patho-genic.

About 5-10% of all ovarian cancer cases show familial clustering, and some 15-25% of familial ovarian cancer cases are mediated by high-penetrance mutations in the BRCA1 and BRCA2 genes. Only few other genes have been identified for familial ovarian cancer.We conducted targeted next-generation sequencing of the protein coding region of 21 candidate genes, including UTR regions, in genomic DNA samples of 48 patients with familial ovarian cancer from the Republic of Bashkortostan. We identified deleterious variants in BRCA1, BRCA2, CHEK2, MSH6 and NBN in a total of 16 patients (33%). The NBN truncating variant, p.W143X, had not previously been reported. Seven patients (15%) were carriers of the c.5266dupC variant in BRCA1, supporting a Russian origin of this founder allele. An additional 15 variants of uncertain clinical significance were observed. We conclude that our gene panel explains about one-third of familial ovarian cancer risk in the Republic of Bashkortostan.

Malignant neoplasms of the ovaries are one of the most frequently diagnosed tumors of the female reproductive system and one of the leading causes of cancer death in women worldwide. Despite significant advances in the field of early diagnosis and treatment of the disease, the survival rate of patients with this form of oncopathology is still low, which dictates the need for further study of this problem. The aim of the work was to evaluate the role of polymorphic variants rs13181 and rs238406 of the ERCC2 gene in the development of hereditary and sporadic forms of ovarian cancer in women of different ethnicity from the Republic of Bashkortostan. The material for the study was DNA samples of women with sporadic forms of ovarian cancer (n=182), hereditary forms of ovarian cancer (n=65) and women without cancer at the time of blood sampling (n=292) of various ethnic origins. Genotyping was performed by polymerase chain reaction (PCR) followed by analysis of restriction fragment length polymorphism. As a result of the study, an association of the rs13181*C allele of the ERCC2 gene with the risk of developing hereditary and sporadic forms of ovarian cancer in women of Russian ethnicity was established. An association of the rs238406*GT genotype of the ERCC2 gene with the risk of developing sporadic forms of ovarian cancer was revealed. The data obtained indicate the involvement of the studied polymorphic variants in the pathogenesis of ovarian cancer in our region.

Being one of the most mountainous Turkic peoples in the world, the genetic background of the Karachais and Balkars remains poorly understood. The aim of this study is to comprehensively study the haplogroup R1a-Z2122 of the Y-chromosome in the population of Karachais and in the sub-ethnic groups of Balkars. The material for the study was DNA samples from Karachais (n = 126) and Balkars (n = 235). The analysis of the genetic diversity of the population of Karachais and subpopulations of Balkars living in the central part of the North Caucasus region was carried out according to the data on the distribution of Y-SNP (Single nucleotide polymorphism) hap-logroups and Y-STR (Short tandem repeats) haplotypes. According to the results of genotyping of the R1a-Z2122 haplogroup in the Balkar subpopulations, the R1a-Z2122 haplogroup was detected with a frequency of 3.4%, and in the Karachai population - 2.4%. In the course of studying the distribution of this haplogroup in sub-ethnic groups of Balkars, its high content in the group of Chegemians was shown, where it is 6.8% of the diversity of haplogroups of the Y-chromosome. In the group of Baksans, the frequency of this haplogroup decreases to 4.8%, among Bezengievs it is found in 2.6% of the population, and among Malkars in 1.7%, while this haplogroup was not found in the Kholam population. For the analysis of STR-haplotypes of the Y-chromosome, we selected 11 samples belonging to the haplogroup R1a-Z2122. As a result of the construction of the median network and the circular dendrogram, significant variability was shown within the studied sample. The data obtained by us as a result of the research can be used in the development of courses for students of biological, historical and medical specialties. The created unique collection of DNA samples from Balkars and Karachais can subsequently be used for population, evolutionary, and medico-genetic studies.

механизмах опухолеобразования яичников и выявить множество новых молекулярных маркеров этого процесса.Однако вклад выявленных вариантов в формирование предрасположенности к РЯ изучен недостаточно и требует проведения дальнейших исследований.Ключевые слова:

The main function of matrix metalloproteinases is the degradation of the extracellular matrix and participation in signal transduction. In addition, it is known that they are involved in all stages of the progression of the tumor process. The activity of metalloproteinases can be regulated by interactions with specific inhibitors of matrix metalloproteinases, so the latter are also able to participate in tumor growth. The genes of matrix metalloproteinases and their inhibitors, as well as many other genes, are characterized by polymorphism. We have analyzed the frequency distribution of the alleles and genotypes of the polymorphic loci rs1799750 and rs494379 of the MMP1 gene, rs2285053 of the MMP2 gene, rs3025058 of the MMP3 gene, rs3918242 and rs17576 of the MMP9 gene, rs2276109 of the MMP12 gene, rs8179090 of the TIMP2 gene, and rs9619311 of the TIMP3 gene in 314 patients with gastric cancer, as well as in 339 unrelated healthy individuals from the Republic of Bashkortostan. It was shown that the markers of the increased risk of developing gastric cancer are the genotypes rs1799750*1G/2G of the MMP1 gene and rs2276109*A/A of the MMP12 gene for Tatars and the genotype rs9619311*T/T of the TIMP3 gene for Russians. The association of the rs494379*G allele of the MMP1 gene and increased risk of developing malignant tumors of the stomach were reported in men. Using the APSampler algorithm, we identified combinations of alleles/genotypes associated with an increased and a reduced risk of developing gastric oncopathologies. The data obtained confirm the influence of the studied polymorphic variants of the genes of matrix metalloproteinases and their tissue inhibitors on the risk of developing gastric cancer and are important for understanding the genetic structure of the studied pathology.

Рак яичников является одним из наиболее распространенных злокачественных новообразований органов репродуктивной системы. В настоящей работе представлен анализ ассоциации rs757210 гена HNF1B с риском развития РЯ у женщин из Республики Башкортостан. Ovarian cancer (OC) is one of the most common malignant neoplasms of the organs of the reproductive system. In this paper, we analyze the associations of polymorphisms rs757210 в of the HNF1B gene with the risk of developing OC in women from the Republic of Bashkortostan.

Проведен анализ распределения частот аллелей/генотипов полиморфных локусов rs1799750 и rs494379 гена MMP1, rs2285053 гена MMP2, rs3025058 гена MMP3, rs3918242 и rs17576 гена MMP9, rs2276109 гена MMP12, rs8179090 гена TIMP2 и rs9619311 гена TIMP3 у 314 пациентов с раком желудка, а также у 339 здоровых индивидов из Республики Башкортостан. С помощью алгоритма APSampler выявлены сочетания аллелей/генотипов, ассоциированные как с повышенным, так и с пониженным риском развития заболевания. The analysis of the frequency distribution of alleles/genotypes of polymorphic loci rs1799750 and rs494379 of the MMP1 gene, rs2285053 of the MMP2 gene, rs3025058 of the MMP3 gene, rs3918242 and rs17576 of the MMP9 gene, rs2276109 of the MMP12 gene, rs8179090 of the TIMP2 gene and rs9619311 of the TIMP3 gene in 314 patients with gastric cancer, as well as in 339 healthy individuals from the Republic of Bashkortostan. Using the APSampler algorithm were identified combinations of alleles/genotypes associated with increased and reduced risk of developing the disease.

Рак яичников (РЯ) представляет собой важную проблему здравоохранения во всем мире. Данная онкопатология имеет самые высокие показатели смертности и самые низкие показатели выживаемости в течение первого года среди злокачественных опухолей женской репродуктивной системы. В связи с этим, разработка и усовершенствование методов ранней диагностики РЯ являются одной из приоритетных задач онкогинекологии. В настоящей работе представлен поиск ассоциаций варианта сайта сплайсинга c.1047-2A> G в гене CDK12 с развитием рака яичников в Республики Башкортостан. Ovarian cancer (OV) is an important public health problem worldwide. This oncopathology has the highest mortality rates and the lowest survival rates during the first year among malignant tumors of the female reproductive system. In this regard, the development and improvement of methods for the early diagnosis of cancer is one of the priority tasks of gynecological oncology. This paper presents a search for associations of a variant of the splicing site c.1047-2A> G in the CDK12 gene with the development of ovarian cancer in the Republic of Bashkortostan.

Pro- and anti-inflammatory cytokines modulate the inflammatory response in the gastric mucosa. The analysis of associations of allelic variants of cytokine genes in the process of tumorous transformation of the gastric mucosa is an urgent problem. Its solution could make it possible to identify the features of production of inflammatory mediators by the immunocompetent cells during gastric carcinogenesis. The frequencies of alleles and genotypes of the rs1143634 and rs16944 loci of the IL1β gene, rs71941886 of the IL1RN gene, rs4073 of the IL8 gene, and rs1800872 of the IL10 gene were analyzed in 221 patients with established diagnosis of gastric cancer, as well as in 279 unrelated healthy individuals from the Republic of Bashkortostan. We discovered an association of the allele С and genotype C/C of the rs1143634 locus of the IL1β gene with a risk of development of malignant tumors of the stomach in men. We identified statistically significant differences in between patients and the control group in the distribution of frequencies of alleles and genotypes of the polymorphic variants: rs16944 of the IL1β gene and rs1800872 of the IL10 gene. Dependence of the associations with clinical features of the disease was also shown. Application of the APSampler algorithm revealed the combinations of alleles and genotypes associated with reduced and increased risk of the development of gastric cancer. The most significant were IL1β (rs1143634)*T + IL1β (rs16944)*T/T, IL8*A + IL10*A + IL1β (rs1143634)*T + IL1β (rs16944)*T, and IL10*A + IL1RN*2/2. The obtained results confirm the influence of the investigated allelic variants of cytokine genes on the risk of developing gastric cancer and play an important role in understanding the genetic structure of the studied pathology.

Introduction. Much attention in ccRCC development is paid to VHL-HIF1α pathway genes. Numerous genes involved in the pathogenesis of ccRCC are targets for miRNA. Alteration in the nature of interaction with miRNA binding site as a result of a single nucleotide substitution may promote change the expression of target genes involved in the genesis and development of tumors.Purpose of research. Analysis of the role of polymorphic variants in the miRNA binding sites of the VHL-HIF1α gene pathways in ccRCC development.Materials and methods. We used 225 DNA samples isolated from the venous blood of ccRCC patients who are hospitalized to the Clinic of the Bashkir State Medical University, and 298 healthy individuals. The genotyping of miRNA binding site polymorphisms in VHL-HIFα-dependent pathway genes (rs10982724 of the DEC1 gene, rs406271 of the TFRC gene, rs10491534 of the TSC1 gene, rs1642742 of the VHL gene, rs3025033 of the VEGFA gene) was performed using Taq-man assays.Results. The frequency distribution of alleles and genotypes of rs1642742 of the VHL gene showed that rs1642742 *GG is a marker of the increased risk for ccRCC. In addition, rs10491534 * C allele was found to be the marker for severe ccRCC (p = 0.044; OR = 1.72 (CI = 1.012-2.911)), and rs10491534 * TT genotype (p = 0.044; OR = 0.55; (95% CI = 0.31–0.98)) of the TSC1 gene was shown to be a protective marker for ccRCC of severe duration.Conclusions. The study indicated the association of miRNA binding sites polymorphisms with the risk of ccRCC development and severity of disease. However, further studies of the genes are needed to establish their functional significance and role in the pathogenesis of ccRCC.

Рак яичников (РЯ) занимает одно из лидирующих мест среди онкопатологии репродуктивной сферы у женщин. Высокие показатели заболеваемости и смертности от данного вида рака свидетельствуют о необходимости более глубокого понимания молекулярно-генетических основ заболевания для разработки новых подходов к диагностике и лечению РЯ. В последнее время при исследовании патогенеза злокачественных новообразований яичников большой интерес ученых во всем мире вызывает изучение роли генов иммунного ответа и воспаления. В статье представлены результаты исследования роли аллельных вариантов генов NFKB1 (rs28362491), IL6 (rs1800795), IL18 (rs1946518) и IL23R (rs7517847, rs10889677) в патогенезе РЯ у женщин из Республики Башкортостан. Материалом для работы послужили образцы ДНК женщин с установленным диагнозом «рак яичников» (n=238) и здоровых индивидов (n=284). Генотипирование образцов ДНК проводили методами полимеразной цепной реакции (ПЦР) с последующим анализом полиморфизма длин рестрикционных фрагментов и аллель-специфичной ПЦР. Установлено, что генетическими маркерами риска развития рака яичников для женщин русской этнической принадлежности пременопаузального возраста являются генотипы rs28362491*ID в гене NFKB1 и rs1946518*СA в гене IL18. Носительство генотипов rs1800795*GG в гене IL6 и rs10889677*CС в гене IL23R для женщин татарской этнической принадлежности в постменопаузе является протективным фактором. Для татар с генотипом rs10889677*CА в гене IL23R в постменопаузе, напротив, было показано повышение риска развития заболевания. К маркерам пониженного риска развития РЯ у русских также можно отнести генотип rs1946518 *AA в гене IL18, который был отмечен как протективный фактор для женщин как в пре-, так и постменопаузе, а также у больных данной онкопатологией с начальными и запущенными стадиями заболевания. При сравнительном анализе распределения частот аллелей и генотипов полиморфного варианта rs7517847 в гене IL23R среди больных РЯ и здоровых доноров статистически значимых различий между исследуемыми группами не обнаружено. Ovarian cancer (OC) is one of the most common malignancyof the female reproductive system. High rates of morbidity and mortality from this type of cancer indicate the need for a deeper understanding of the molecular genetic basis of the disease, which in turn will contribute to the development of new approaches to the diagnosis and treatment of OC. Recently, when studying the pathogenesis of malignant neoplasms of the ovaries, a great interest of scientists around the world is directed to studying the role of the immune response and inflammation genes in the development of the OC. At this work presents the results of the study of the role of the polymorphic loci of the genes NFKB1 (rs28362491), IL6 (rs1800795), IL18 (rs1946518) and IL23R (rs7517847, rs10889677) in the pathogenesis of ovarian cancer in women from the Republic of Bashkortostan.The material for the work was the DNA samples of women with an established diagnosis of ovarian cancer (n = 238) and healthy individuals (n = 284). Genotyping of DNA samples was performed using polymerase chain reaction (PCR), followed by analysis of restriction fragment length polymorphism and allele-specific PCR. It has been established that the genetic markers of the risk of developing ovarian cancer for women of Russian ethnicity at premenopausal age are the genotypes rs28362491* ID in the NFKB1 gene and rs1946518 * CA in the IL18 gene. The carrier of the rs1800795 * GG genotypes in the IL6 gene and rs10889677 * CС in the IL23R gene for post-menopausal women of Tatar ethnicity is a protective factor. For Tatars with the rs10889677 * CA genotype in the IL23R postmenopausal gene, on the contrary, an increased risk of developing the disease was shown. Markers of a reduced risk of developing ovarian cancer in Russians can also include the rs1946518 * AA genotype in the IL18 gene, which was noted as a protective factor for women in both pre- and postmenopausal women, as well as in patients with this oncopathology with initial and advanced stages of the disease. A comparative analysis of the frequency distribution of alleles and genotypes of the polymorphic variant rs7517847 in the IL23R gene among patients with OC and healthy donors did not reveal statistically significant differences between the studied groups.

Purpose of the study. To evaluate the clinical and genetic picture of patients with duodenal ulcer. Materials and research methods. A total of 139 patients with duodenal ulcer were examined. Of these, hereditary predisposition groups (n = 102) and without it (n = 129) were selected, which were examined according to standards, including the analysis of polymorphic variants of IL8 genes (–251T>A; rs4073) , IL10 (–627 С > A; rs1800872) , TNFA (–308G> A ; rs1800629) , the gene for antagonist to the IL1 receptor (IL1RN (VNTR); rs71941886)) by PCR, investigated the psychological status. Results. Patients with a genetic predisposition were found to have the first blood group, non-compliance with the diet, threshold resistance to stress, lack of family life, the presence of duodeno-gastric reflux, gross deformity of the bulb, increased acidity, men had more frequent night work, smoking, alcohol intake, medium-specific education. In patients, the rs1800872 * AA genotype and the rs1800872 * A allele of the IL10 gene (–627 С > A; rs1800872) are markers of the development of duodenal ulcer. Conclusion. Conducting genetic studies of individuals along with clinical examinations contributes to an integrated approach in the management of individuals with duodenal ulcer.