Abstract
BRCA1-associated breast cancers are associated with particular features such as early onset, poor histological differentiation, and hormone receptor negativity. Previous studies conducted in Taiwanese population showed that the mutation of BRCA1 gene does not play a significant role in the occurrence of breast cancer. The present study explored methylation of BRCA1 promoter and its relationship to clinical features and outcome in Taiwanese breast cancer patients. Tumor specimens from a cohort of 139 early-stage breast cancer patients were obtained during surgery before adjuvant treatment for DNA extraction. Methylation of BRCA1 promoter region was determined by methylation-specific PCR and the results were related to clinical features and outcome of patients using statistical analysis. Methylation of the BRCA1 promoter was detected in 78 (56%) of the 139 tumors. Chi-square analysis indicated that BRCA1 promoter methylation correlated significantly with triple-negative (ER-/PR-/HER2-) status of breast cancer patients (p = 0.041). The Kaplan-Meier method showed that BRCA1 promoter methylation was significantly associated with poor overall survival (p = 0.026) and disease-free survival (p = 0.001). Multivariate analysis which incorporated variables of patients' age, tumor size, grade, and lymph node metastasis revealed that BRCA1 promoter methylation was associated with overall survival (p = 0.27; hazard ratio, 16.38) and disease-free survival (p = 0.003; hazard ratio, 12.19). Our findings underscore the clinical relevance of the methylation of BRCA1 promoter in Taiwanese patients with early-stage breast cancer.
Highlights
Breast cancer is the most common type of cancer and ranked fourth in cancer mortality in Taiwan [1]
Consistent with the methylation status of BRCA1 promoter, the expression levels of BRCA1 protein were reduced in tumors with methylated genes (Figure 1B)
We report here that hypermethylation of the BRCA1 gene promoter is present in 56% (78 of 139) of Taiwanese women with early-stage sporadic breast carcinomas, which is significantly higher than previously reported frequencies for this
Summary
Breast cancer is the most common type of cancer and ranked fourth in cancer mortality in Taiwan [1]. Incidence of breast cancer in Taiwan has been increasing steadily and the rise can be largely attributed to the rise of newly diagnosed young patients [2]. BRCA1 is a major cancer predisposition gene that has been the subject of intense investigation since it was identified and cloned in 1994 [3]. Breast tumors arising from BRCA1 mutation acquired distinct pathological and gene expression profiles [4]. The spectrum of BRCA1 gene mutations in breast cancer patients in various populations has been investigated [5,6,7,8,9,10]. Studies conducted in Taiwan had suggested that the mutation of BRCA1 contributes little to the occurrence of breast cancer [11,12]
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