ArticleCancer prevention research (Philadelphia, Pa.)2011
Constitutional methylation of the BRCA1 promoter is specifically associated with BRCA1 mutation-associated pathology in early-onset breast cancer.
Article in Cancer prevention research (Philadelphia, Pa.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 6 of them syntheses that pooled it.
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90 citing papers in PubMed, 6 syntheses or guidelines pooled it, 164 citations in OpenAlex.
- Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies.Breast cancer research : BCR · 2022Pooled it
- Pooled it
- Blood DNA methylation and breast cancer risk: a meta-analysis of four prospective cohort studies.Breast cancer research : BCR · 2019Pooled it
- Association of BRCA1 Promoter Methylation with Breast Cancer in Asia: A Meta- AnalysisAsian Pacific journal of cancer prevention : APJCP · 2018Pooled it
- Blood-based DNA methylation as biomarker for breast cancer: a systematic review.Clinical epigenetics · 2016Pooled it
- Association of BRCA1 promoter methylation with sporadic breast cancers: Evidence from 40 studies.Scientific reports · 2015Pooled it
- Olaparib in HR-deficient, metastatic triple-negative breast and platinum-sensitive relapsed ovarian cancers without germline mutations in BRCA1/2: phase 2 EMBRACE trial.British journal of cancer · 2026Trial
- Prevalence ofJCO precision oncology · 2026Article
- Development and validation of an 11-CpG methylation signature-based nomogram for predicting prognosis in early-onset breast cancer.Translational cancer research · 2026Article
- Methylation differences between assisted reproductive technology-conceived and naturally conceived children nearEpigenetics · 2025Article
- Constitutional epimutations in LTBP4, a component of the TGF-β signaling, and in BRCA1, as potential drivers of early-onset colorectal cancer.Clinical epigenetics · 2025Article
- Constitutional Epimutations: From Rare Events Toward Major Cancer Risk Factors?JCO precision oncology · 2025Review
- High-level tumour methylation ofNAR cancer · 2024Article
- DNA methylation in necrotizing enterocolitis.Expert reviews in molecular medicine · 2024Review
- The role of aberrant DNA methylation in cancer initiation and clinical impacts.Therapeutic advances in medical oncology · 2024Article
- ConstitutionalHuman mutation · 2024Review
- Unraveling noncoding DNA variants and epimutations: a paradigm shift in hereditary cancer research.Future oncology (London, England) · 2024Review
- Prenatal BRCA1 epimutations contribute significantly to triple-negative breast cancer development.Genome medicine · 2023Article
- Contribution of constitutional BRCA1 promoter methylation to early-onset and familial breast cancer patients from Pakistan.Breast cancer research and treatment · 2023Article
- Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study.NPJ breast cancer · 2023Article
30 more citing papers are in PubMed but not listed here.
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9 authors at 4 institutions in 1 country.
Funding
Abstract
Women carrying germline mutations in BRCA1 are at a substantially elevated risk of breast cancer and their tumors typically have distinctive morphologic features. We hypothesized that constitutional methylation of the BRCA1 promoter region could give rise to such breast cancers in women. We selected 255 women diagnosed with breast cancer before the age of 40 years for whom BRCA1 germline mutations had not been identified. Of them, 52 had five or more of nine BRCA1 mutation-associated morphologic features (group 1), 39 had four (group 2), and 164 had three or less (group 3). The prevalence of detectable BRCA1 promoter methylation in peripheral blood DNA decreased from 31% to 10% to 5% across groups 1-3, respectively (P = 0.000002), and was significantly greater than the 4% frequency in unaffected controls (P = 0.004). Peripheral blood methylation was associated with a 3.5-fold (95% CI, 1.4-10.5) increased risk of having early onset breast cancer. Methylation was consistently mosaic in the peripheral blood where the estimated allelic frequency of BRCA1 promoter methylation ranged from 0.1% to 17%. Group 1 women, but not group 3 women, with detectable methylation of peripheral blood DNA had high levels of BRCA1 promoter methylation of their tumor DNA, indicating that constitutional BRCA1 methylation strongly predisposes toward the development of BRCA1 methylated tumors that then have features resembling BRCA1 mutated tumors. Screening peripheral blood for BRCA1 promoter methylation might thus predict early-onset breast cancers. This raises the possibility of chemoprevention or other intervention to diminish the risk of developing breast cancer in these women.
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