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The breast cancer susceptibility gene 1 (  BRCA 1 ) and glutathione S‐transferase P1 (  GSTP 1 ) promoters are reportedly often methylated in breast cancer tissues. Their methylation status in surrounding normal breast tissues has not been examined thoroughly although this may well be important for a better understanding of breast carcinogenesis. In this study,   BRCA 1  and   GSTP 1  promoter methylation was examined by methylation‐specific  PCR  assay. Patients with   BRCA  1‐methylated ( n  = 15) or   BRCA  1‐unmethylated ( n  = 15) tumors and those with   GSTP 1 ‐methylated ( n  = 9) or   GSTP 1 ‐unmethylated ( n  = 11) tumors were included in the present study. Methylation status of manually micro‐dissected normal epithelial cells from the formalin‐fixed paraffin‐embedded sections of normal breast tissues adjacent to and distant from the tumors was examined at multiple sites ( n  = 1–5). Of the 15 patients with   BRCA 1 ‐methylated tumors, 9 harbored   BRCA 1  promoter methylation in at least one site of the normal breast tissues. However, no   BRCA 1  promoter methylation was observed at any site of the normal tissues of the 15 patients with   BRCA 1 ‐unmethylated tumors. No   GSTP 1  promoter methylation was observed in the normal tissues regardless of the methylation status of the tumors. The presence of   BRCA 1  promoter methylation in the normal tissues was confirmed in the epithelial cells enriched with the magnetic‐activated cell sorting method. Our findings suggest that a small proportion of normal breast epithelial cells with   BRCA 1  promoter methylation can be precursor cells from which   BRCA 1 ‐methylated breast tumors may originate. This does not apply to   GSTP 1  promoter methylation.

BRCA 1 promoter methylation of normal breast epithelial cells as a possible precursor for BRCA 1 ‐methylated breast cancer