RESUMO
BACKGROUND: The BRCA1 mutations that are endemic to the Slavic population of Russia have not been identified among indigenous peoples, including the Buryats, Tuvinians and Altaians with hereditary breast cancer. OBJECTIVE: This study was aimed to identify the mutations that are responsible for the occurrence of hereditary breast cancer in the indigenous population of the Republic of Buryatia. METHODS: Mutations in the BRCA1 gene were identified in blood samples by Sanger-based sequencing. RESULTS: We identified 11 polymorphisms (10 SNPs and 1 Indel) and 6 new unclassified sequence variants in the BRCA1 gene. In our study three new sequence variants (c.321T>A, c.366T>A, c.4357+2T>A) were found in position of previously described polymorphisms in dbSNPs: rs80357544 (c.321delT), rs190900046 (c.366T>G), and rs80358152 (c.4357+2T>C), respectively. Other three new sequence variants (c.3605A>G, c.1998A>C, and c.80+13A>C) have not been previously described in dbSNP, BIC and Human Gene Mutation Databases. CONCLUSIONS: We described six new sequence variants that have never been published in the literature or databases. Further studies are required to confirm the impact of new sequence variants on the risk of breast cancer in the Buryat Mongol population.
Assuntos
Proteína BRCA1/genética , Neoplasias da Mama/genética , Variação Genética , Alelos , Substituição de Aminoácidos , Feminino , Genótipo , Geografia , Humanos , Mutação , Linhagem , Polimorfismo de Nucleotídeo Único , Federação Russa , Análise de Sequência de DNARESUMO
BACKGROUND: Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice has shown great promise to provide personalized therapy of the non-small cell lung cancer (NSCLC) in the developed world. However, the genetic testing of EGFR mutations has not yet become routine clinical practice in territories remote from the central regions of Russia. Therefore, we aimed to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients residing in West Siberia. MATERIALS AND METHODS: We examined EGFR mutations in exons 19 and 21 in 147 NSCLC patients (excluding squamous cell lung carcinomas) by real time polymerase chain reaction. RESULTS: EGFR mutations were detected in 28 of the 147 (19%) patients. There were 19 (13%) cases with mutations in exon 19 and 9 cases (6%) in exon 21. Mutations were more frequently observed in women (42%, p=0.000) than in men (1%). A significantly higher incidence of EGFR mutations was observed in bronchioloalveolar carcinomas (28%, p=0.019) and in adenocarcinomas (21%, p=0.024) than in large cell carcinomas, mixed adenocarcinomas, and NOS (4%). The EGFR mutation rate was much higher in never-smokers than in smokers: 38% vs. 3% (p=0.000). The frequency of EGFR mutations in the Kemerovo and Tomsk regions was 19%. CONCLUSIONS: The incorporation of molecular analysis of the EGFR gene into routine clinical practice will allow clinicians to provide personalised therapy, resulting in a significant increase in survival rates and improvement in life quality of advanced NSCLC patients.
Assuntos
Adenocarcinoma Bronquioloalveolar/genética , Carcinoma de Células Grandes/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Mutação/genética , Adenocarcinoma Bronquioloalveolar/patologia , Adulto , Idoso , Carcinoma de Células Grandes/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Testes Genéticos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Federação RussaRESUMO
AIM: To investigate the potential of the anti-oxidant ascorbic acid glucoside (AA-2G) to modulate neurotoxicity induced by high doses of nitrotriazole radiosensitizer. MATERIALS AND METHODS: Male and female C56Bl/6xCBA hybrid mice aged 8-14 weeks (weight 18-24 g) were used. Nitrotriazole drug radiosensitizer sanazole at a high dose of 2, 1 g/kg was per os administered to induce neurotoxicity at mice. Ascorbic acid glucoside was given 30 min before the sanazole administration. Serum ascorbic acid, brain glutathione level, as well as behavioral performance using open field apparatus were measured. RESULTS: Administration of high (non-therapeutic) doses of the nitrotriazole drug sanazole results in neurotoxicity in mice as evidenced from behavioral performance, emotional activity and depletion of the cellular antioxidant, glutathione, in the brain. The serum levels of ascorbic acid was also found reduced in high dose sanazole treated animals. Per os administration of ascorbic acid glucoside significantly reduced the neurotoxicity. This effect was associated with the prevention of glutathione depletion in mouse brain and restoring the ascorbic acid level in serum. CONCLUSION: Administration of ascorbic acid glucoside, but not ascorbic acid, before sanazole administration protected from sanazole-induced neurotoxicity by preventing the decrease in the brain reduced glutathione level and providing high level of ascorbic acid in plasma.