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BRCA1 promoter methylation in peripheral blood is associated with the risk of triple-negative breast cancer |
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| Authors: | Karolina Prajzendanc Paweł Domagała Jolanta Hybiak Janusz Ryś Tomasz Huzarski Marek Szwiec Joanna Tomiczek-Szwiec Wojciech Redelbach Aleksandra Sejda Jacek Gronwald Tomasz Kluz Rafał Wiśniowski Cezary Cybulski Alicja Łukomska Katarzyna Białkowska Grzegorz Sukiennicki Katarzyna Kulczycka Steven A. Narod Tomasz K. Wojdacz Jan Lubiński Anna Jakubowska |
| Affiliation: | 1. Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland;2. Department of Pathology, Pomeranian Medical University, Szczecin, Poland;3. Department of Tumor Pathology, Maria Skłodowska-Curie Memorial Centre and Institute of Oncology, Cracow, Poland;4. Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland Department of Clinical Genetics and Pathology, University of Zielona Góra, Zielona Góra, Poland;5. Department of Surgery and Oncology, University of Zielona Góra, Zielona Góra, Poland Department of Clinical Oncology, University Hospital in Zielona Góra, Zielona Góra, Poland;6. Department of Histology, Institute of Medicine, University of Opole, Opole, Poland Regional Oncology Centre, Opole, Poland;7. Department of Anatomy, Institute of Medicine, University of Opole, Opole, Poland;8. Department of Pathology, Provincial Specialist Hospital, Olsztyn, Poland Patomorphology Department, University of Warmia and Mazury, Olsztyn, Poland;9. Institute of Obstetric and Emergency Medicine, Faculty of Medicine, University of Rzeszow, Rzeszow, Poland;10. Department of Clinical Oncology, Regional Oncology Centre, Bielsko-Biala, Poland;11. Women's College Research Institute, Women's College Hospital, Toronto, ON, Canada;12. Independent Clinical Epigenetics Laboratory, Pomeranian Medical University, Szczecin, Poland |
| Abstract: | Methylation of the promoter of the BRCA1 gene in DNA derived from peripheral blood cells is a possible risk factor for breast cancer. It is not clear if this association is restricted to certain types of breast cancer or is a general phenomenon. We evaluated BRCA1 methylation status in peripheral blood cells from 942 breast cancer patients and from 500 controls. We also assessed methylation status in 262 paraffin-embedded breast cancer tissues. Methylation status was assessed using methylation-sensitive high-resolution melting and was categorized as positive or negative. BRCA1 methylation in peripheral blood cells was strongly associated with the risk of triple-negative breast cancer (TNBC) (odds ratio [OR] 4.70; 95% confidence interval [CI]: 3.13–7.07; p < 0.001), but not of estrogen-receptor positive breast cancer (OR 0.80; 95% CI: 0.46–1.42; p = 0.46). Methylation was also overrepresented among patients with high-grade cancers (OR 4.53; 95% CI: 2.91–7.05; p < 0.001) and medullary cancers (OR 3.08; 95% CI: 1.38–6.88; p = 0.006). Moreover, we detected a significant concordance of BRCA1 promoter methylation in peripheral blood and paired tumor tissue (p < 0.001). We found that BRCA1 promoter methylation in peripheral blood cells is associated with approximately five times greater risk of TNBC. We propose that BRCA1 methylation in blood-derived DNA could be a novel biomarker of increased breast cancer susceptibility, in particular for triple-negative tumors. |
| Keywords: | methylation in peripheral blood BRCA1 gene TNBC |