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Promoter hypermethylation was shown to be involved in human cancerogenesis through silencing gene expression. Several studies were dedicated to explore the frequency and clinical significance of BRCA1 hypermethylation in sporadic breast cancer to identify a specific molecular and clinico-pathological phenotype. However the available data are limited and rather too heterogeneous. In this study we investigated the level of methylation in the promoter region of BRCA1 and its correlation with clinico-pathological and molecular characteristics in a group of 135 Bulgarian patients. Methylation specific PCR was applied to determine methylation status of tumor samples. Clinical impact of BRCA1 hypermethylation was estimated using standard statistical methods including Fisher's exact and the Chi-squared tests, the Kaplan-Meier method, the univariate and multivariate Cox proportional hazards regression model. We found that hypermethylation was present in 17.04% of the cases (23/135). Patients with hypermethylation in BRCA1 displayed favorable clinical status as their tumors were smaller in size (P = 0.066), lacked p53 gene mutations (P = 0.073) and were of lobular type (P = 0.046). The presence of hypermethylation was weakly associated with better overall survival (P = 0.2) with a hazard ratio of 0.47 (95% CI 0.14-1.54, P= 0.213). Our study provides the first data on the BRCA1 hypermethylation of Bulgarian patients and contributes to elucidation of its clinical significance in sporadic breast cancer.

Breast cancer patients with hypermethylation in the promoter of BRCA1 gene exhibit favorable clinical status