JAMA Oncology (2022): Constitutional BRCA1 Methylation and Risk of Incident Triple-Negative Breast Cancer and High-grade Serous Ovarian Cancer Using Methyl Detect Technology

Background: This nested case-control study utilized massive parallel sequencing following bisulfite conversion to assess white blood cell (WBC) genomic DNA from Women’s Health Initiative participants. By evaluating 4 overlapping regions covering the BRCA1 promoter area, the assay measured variant epiallele frequency (VEF) to determine constitutional promoter methylation status and its relationship to subsequent cancer risk.
Key Finding: The presence of methylated BRCA1 alleles in white blood cells was significantly associated with an increased risk of incident triple-negative breast cancer (TNBC) (HR, 2.35; 95% CI, 1.70-3.23; P < .001) and high-grade serous ovarian cancer (HGSOC) (HR, 1.93; 95% CI, 1.36-2.73; $P < .001$ ). These associations remained statistically significant even when restricting analyses to individuals diagnosed more than 5 years after blood sampling.
Conclusion: Constitutional normal tissue BRCA1 promoter methylation serves as an important predisposing risk factor for incident TNBC and HGSOC, demonstrating potential for early cancer prediction, patient stratification, and precision oncology biomarker development.
Original Article & Authors: Published in JAMA Oncology (2022), authored by Per E. Lønning, Oleksii Nikolaienko, Kathy Pan, Allison W. Kurian, Hans P. Eikesdal, Mary Pettinger, Garnet L. Anderson, Ross L. Prentice, Rowan T. Chlebowski, and Stian Knappskog. Research institutions and departments include the K.G. Jebsen Centre for Genome-Directed Cancer Therapy and Department of Clinical Science at the University of Bergen, Department of Oncology at Haukeland University Hospital (Bergen, Norway), Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Stanford University, and the Fred Hutchinson Cancer Center.

Read the full publication, see the link below ↓