Abstract
Epigenetic modifications are involved in breast carcinogenesis. Identifying genes that are epigenetically silenced via methylation could select target patients for diagnostic as well as therapeutic potential. We assessed promoter methylation of breast cancer susceptibility gene 1 (BRCA1) and 17 Beta Hydroxysteroid Dehydrogenase Type 1 (17βHSD-1) in normal and cancer breast tissues of forty sporadic breast cancer (BC) cases using restriction enzyme based methylation-specific PCR (REMS-PCR). In cancerous tissues, BRCA1 and 17βHSD-1 were methylated in 42.5% and 97.5%, respectively, while normal tissues had 35% and 95% methylation, respectively. BRCA1 methylation in normal tissues was 12.2-fold more likely to associate with methylation in cancer tissues (p < 0.001). It correlated significantly with increased age at menopause, mitosis, the negative status of Her2, and the molecular subtype “luminal A” (p = 0.048, p = 0.042, p = 0.007, and p = 0.049, resp.). Methylation of BRCA1 and 17βHSD-1 related to luminal A subtype of breast cancer. Since a small proportion of normal breast epithelial cells had BRCA1 methylation, our preliminary findings suggest that methylation of BRCA1 may be involved in breast tumors initiation and progression; therefore, it could be used as a biomarker for the early detection of sporadic breast cancer. Methylation of 17βHSD-1 in normal and cancer tissue could save patients the long term use of adjuvant antiestrogen therapies.
Highlights
Breast cancer is a malignancy arising from the epithelial tissues that line the terminal ductal-lobular units of the breast [1, 2]
We found a trend towards breast cancer susceptibility gene 1 (BRCA1) and 17βHSD-1 promoter hypermethylation in cancer tissue specimens of sporadic breast cancer patients compared with controls, the difference was nonsignificant (p > 0.05)
BRCA1 promoter hypermethylation is implicated as one of the mechanisms of loss of gene expression [33]. It was identified in 9–44% of sporadic breast cancers [19,20,21]
Summary
Breast cancer is a malignancy arising from the epithelial tissues that line the terminal ductal-lobular units of the breast [1, 2]. Based on data from the National Cancer Registry Program of Egypt (NCRP) in 2008–2011, BC is the most common malignancy among Egyptian females. It constituted 32.0% of all cancer cases [5]. The majority of promoter cytosine phosphate guanosine (CpG) islands are protected from this epigenetic event; they are unmethylated. In cancer cells, several promoter CpG islands are hypermethylated and form a closed repressive chromatin configuration that affects the transcription initiation of the corresponding genes [11,12,13]. Promoter methylation is a common epigenetic mechanism to silence genes during breast cancer development [14]
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