RESUMO
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.
Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Humanos , Feminino , Bashkiria , Proteína BRCA1/genética , Genes BRCA2 , Mutação , Neoplasias Ovarianas/genética , Carcinoma Epitelial do Ovário/genética , Sequenciamento de Nucleotídeos em Larga Escala , Predisposição Genética para Doença , Neoplasias da Mama/genéticaRESUMO
Peptic ulcer disease is a chronic disease of the gastrointestinal tract, mainly manifesting itself in the formation of the fairly persistent ulcer defect of the mucous membrane of the stomach and/or duodenum. Association analysis of common polymorphisms of matrix metalloproteinases genes MMP-1 (rs1799750, rs494379), MMP-2 (rs2285052), MMP-3 (rs3025058), MMP-9 (rs3918242, rs17576), and MMP-12 (rs2276109) and their tissue inhibitors TIMP-2 (rs8179090) and TIMP-3 (rs9619311) was carried out in 353 patients with a gastric ulcer or duodenal ulcer and in 325 unrelated healthy individuals from the Republic of Bashkortostan. Associations of polymorphic variants rs1799750 and rs494379 of gene MMP-1, rs3025058 of gene MMP-3, rs3918242 and rs17576 of gene MMP-9, and rs9619311 of gene TIMP-3 with the risk of peptic ulcer disease in Russians and Tatars were revealed.
Assuntos
Alelos , Metaloproteinases da Matriz/genética , Úlcera Péptica/genética , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-3/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bashkiria , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/etnologia , Polimorfismo de Nucleotídeo Único , TartaristãoRESUMO
Peptic ulcer disease (PUD) is a chronic disease based on recurrent gastric or duodenal ulcers. Association analysis of common polymorphisms of the cytokines genes IL1B (rs1143634), IL1RN (rs71941886), IL8 (rs4073), IL10 (rs1800872), and TNFA (rs1800629) was conducted in 254 patients with gastric ulcer or duodenal ulcer and in 277 unrelated healthy individuals from the Bashkortostan Republic. Associations of the rs1143634C allele and the C/C genotype of the IL1B gene with PUD in ethnic Bashkirs have been revealed. The frequency of the rs4073A/A genotype of the IL8 gene was significantly higher in the control group as compared to patients infected with H. pylori. Our results confirm the significant role of rs1143634 of the IL1B gene in PUD development.