Molecular characterization of BRCA1 with clinico-pathological features among the breast cancer patients of Eastern India

Abstract

Background: BRCA1, a tumour suppressor gene is found responsible for majority of breast cancer cases of familial history. Its involvement in sporadic breast cancer cases of Bengali population is still an area that requires further research. In the present study, we carried out genetic and clinic-pathological characterization of breast cancer in this population. Methods: We analysed 231 patients of breast cancer from a tertiary cancer centre, Kolkata. The clinical characteristics with histological typing and immunohistochemical staining were studied. BRCA1 mutations were detected by AS-PCR and direct sequencing. To predict the functional effect of novel mutations in BRCA1, in-silico analysis and m-RNA folding was performed. Results: The median age of breast cancer in our study is 49 years. Mutations were identified in 7.36% (n = 17) patients. The mutations are 5382insC (n = 7); c.5237A > C (n = 1);c.5210 G > A(n = 1); UTR-17insg(n = 3); UTR -17ins g and UTR-13g > c(n = 2), UTR-13g > c(n = 1), c.75C > A(n = 1) and c.4675 + 1G > A (n = 1). c.5237A > C and c.5210 G > A mutations have not previously reported. in-silico analysis and m-RNA folding revealed that both the novel mutations probably alters the structure and reduces the protein stability of BRCA1.We found that the tumor histology, grade and tumor size were directly related with node positivity (p = 0.05, p = 0.0001 & p = 0.001 respectively). Age (p = 0.004), tumor grade (p = 0.05), tumor size (p = 0.01) were highly associated with the number of lymph node metastasis. Patients having BRCA mutations are significantly younger than noncarriers. Family history and Laterality of breast cancer identified in BRCA carriers was significantly higher than in noncarriers. Conclusion: This study has shown that genetic and clinical factors are mainly responsible for systematic progression. These results enable improvement in genetic counselling and clinical management of mutation positive families and as well as subsequent testing of family members.