Abstract
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.
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TKW would like to thank Lundbeck Foundation and Danish Cancer Society for the support of this work. This study was supported by the State Committee for Scientific Research Grants: PBZ-KBN-042/P05/2001 and PBZ-KBN-122/P05/02
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The authors declare that they have no conflict of interest
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Tomasz K. Wojdacz and Anna Jakubowska have contributed equally to the publication.
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Gupta, S., Jaworska-Bieniek, K., Narod, S.A. et al. Methylation of the BRCA1 promoter in peripheral blood DNA is associated with triple-negative and medullary breast cancer. Breast Cancer Res Treat 148, 615–622 (2014). https://doi.org/10.1007/s10549-014-3179-0
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DOI: https://doi.org/10.1007/s10549-014-3179-0