Methylation of the BRCA1 promoter in peripheral blood DNA is associated with triple-negative and medullary breast cancer.
It has been proposed that methylation signatures in blood-derived DNA may correlate with cancer risk. In this study, we evaluated whether methylation of the promoter region of the BRCA1 gene detectable in DNA from peripheral blood cells is a risk factor for breast cancer, in particular for tumors with pathologic features characteristic for cancers with BRCA1 gene mutations. We conducted a case-control study of 66 breast cancer cases and 36 unaffected controls. Cases were triple-negative or of medullary histology, or both; 30 carried a constitutional BRCA1 mutation and 36 did not carry a mutation. Blood for DNA methylation analysis was taken within three months of diagnosis. Methylation of the promoter of the BRCA1 gene was measured in cases and controls using methylation-sensitive high-resolution melting (MS-HRM). A sample with any detectable level of methylation was considered to be positive. Methylation of the BRCA1 promoter was detected in 15 of 66 cases and in 2 of 36 controls (OR 5.0, p = 0.03). Methylation was present in 15 of 36 women with breast cancer and without germline BRCA1 mutation, but in none of 30 women with breast cancer and a germline mutation (p < 0.01). The association between methylation and breast cancer was restricted to women with no constitutional BRCA1 mutation (OR 12.1, p = 0.0006). Methylation of the promoter of the BRCA1 gene detectable in peripheral blood DNA may be a marker of increased susceptibility to triple-negative or medullary breast cancer.
Department of Genetics and Pathology, International Hereditary Cancer Centre, Pomeranian Medical University, Szczecin, Poland.
Satish
S
Gupta
Katarzyna
K
Jaworska-Bieniek
Steven A
SA
Narod
Jan
J
Lubinski
Tomasz K
TK
Wojdacz
Anna
A
Jakubowska
D000328:Adult; D019313:BRCA1 Protein / Q000097:blood / Q000235:genetics*; D018276:Carcinoma, Medullary / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D015257:DNA-Cytosine Methylases / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D011401:Promoter Regions, Genetic; D064726:Triple Negative Breast Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology
D019313:BRCA1 Protein; D015257:DNA-Cytosine Methylases