RESUMO
BACKGROUND: The BRCA2 gene is an important tumour suppressor in breast cancer, and alterations in BRCA2 may lead to cancer progression. The aim of the study was to investigate the association of hypermethylation of the BRCA2 gene promoter and its co-hypermethylation with the BRCA1 gene promoter with the development and course of breast cancer in women. METHODS: This study included 74 women with breast cancer (tumour tissue samples and peripheral blood) and 62 women without oncological pathology (peripheral blood) - control group. RESULTS: Hypermethylation of the BRCA2 gene was significantly more frequently detected in the tumour tissue of women with breast cancer compared to their peripheral blood and peripheral blood of control subjects (p= 0.0006 and p= 0.00001, respectively). Hypermethylation of BRCA2 was more frequently detected in patients with breast cancer over the age of 50 and in patients with higher Ki67 expression levels (p= 0.045 and p= 0.045, respectively). There was a high frequency of unmethylated BRCA1 and BRCA2 gene combination in women of the control group compared to women with breast cancer, both in blood samples and tumour tissue samples (p= 0.014 and p= 0.00001, respectively). CONCLUSION: Our study confirms the hypothesis that BRCA2 hypermethylation plays an important role in the pathogenesis of breast cancer and the importance of assessing its co-hypermethylation with BRCA1 in predicting the course of the disease.
Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Metilação de DNA , Regiões Promotoras Genéticas , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Adulto , Proteína BRCA1/genética , Proteína BRCA2/genética , Idoso , Biomarcadores Tumorais/genética , Estudos de Casos e ControlesRESUMO
PURPOSE: The aim of this study was to assess the clinical significance of RUNX3 gene hypermethylation in the pathogenetic mechanisms of breast cancer in women, taking into account its cohypermethylation with the BRCA1 gene. METHODS: This study included 74 women with newly diagnosed breast cancer (samples from female primary breast carcinomas and paired peripheral blood samples) and 62 women without oncological pathology-control group (peripheral blood samples). Epigenetic testing for hypermethylation status studying was performed in all samples on freshly collected material with the addition of a preservative before the storage and DNA isolation. RESULTS: Hypermethylation of the RUNX3 gene promoter region was detected in 71.6% samples of breast cancer tissue and in 35.13% samples of blood. The RUNX3 gene promoter region hypermethylation was significantly higher among breast cancer patients compared to the control group. The frequency of cohypermethylation in RUNX3 and BRCA1 genes was significantly increased in breast cancer tissues compared to the blood of patients. CONCLUSION: A significantly increased frequency of the hypermethylation of the RUNX3 gene promoter region and its cohypermethylation with the BRCA1 gene promoter region was found in tumor tissue and blood samples from patients with breast cancer, in contrast to the control group. The identified differences indicate the importance of further investigations of suppressor genes cohypermethylation in patients with breast cancer. Further large-scale studies are needed to find out whether the detected hypermethylation and cohypermethylation of the RUNX3 gene promoter region will have an impact on the treatment strategy in patients.
Assuntos
Neoplasias da Mama , Carcinoma , Feminino , Humanos , Proteína BRCA1/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma/genética , Relevância Clínica , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Subunidade alfa 3 de Fator de Ligação ao Core/metabolismo , Metilação de DNA , Genes BRCA1 , Regiões Promotoras GenéticasRESUMO
BACKGROUND: In this study, we compared the contribution of pathogenic variants of the BRCA1/2 genes (5382insC, 185delAG, 6174delT, 4153delA, T300G) and hypermethylation of the BRCA1 gene promoter region to the risk of breast cancer and clinical features in women. METHODS: This study enrolled 74 women (tumor tissue, blood) with newly diagnosed breast cancer and 62 women (blood) without oncological pathology (control group). Molecular genetic testing of samples and determination of hypermethylation status were performed on freshly collected material with the addition of a preservative before the procedure of DNA isolation. RESULTS: Hypermethylation of the BRCA1 gene promoter in women is a risk breast cancer factor (χ2 = 19.10, p = 0.001, OR = 16.25 (3.67-71.92)) and is more common than major pathogenic variants in the BRCA1/2 genes. The patients with the BRCA1 gene promoter hypermethylation were more likely to be diagnosed with late-stage metastatic cancer (χ2 = 4.31, p = 0.038, OR = 4.04 (1.19-13.65)). Hypermethylation of the BRCA1 gene promoter was predominant in tumor tissue among BC patients without family history compared to patients with cancer in relatives. CONCLUSION: We proved that hypermethylation of the BRCA1 gene promoter is a risk factor for breast cancer and possibly an early biological marker of clinical onset, as its presence contributed to rapid disease progression with metastasis. The high frequency of hypermethylation in the examined breast cancer patients may be a consequence of environmental factors pressure on the risk of the disease development. Further large-scale studies are needed for the clinical application of the results.