ArticleGenome medicine2014
A BRCA1-mutation associated DNA methylation signature in blood cells predicts sporadic breast cancer incidence and survival.
Article in Genome medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Article
- MethAgingDB: a comprehensive DNA methylation database for aging biology.Scientific data · 2025Article
- Impact of BRCA mutations, age, surgical indication, and hormone status on the molecular phenotype of the human Fallopian tube.Nature communications · 2025Article
- Pre-diagnosis blood DNA methylation profiling of twin pairs discordant for breast cancer points to the importance of environmental risk factors.Clinical epigenetics · 2024Article
- Exploring cross-tissue DNA methylation patterns: blood-brain CpGs as potential neurodegenerative disease biomarkers.Communications biology · 2024Article
- DNA methylation at quantitative trait loci (mQTLs) varies with cell type and nonheritable factors and may improve breast cancer risk assessment.NPJ precision oncology · 2023Article
- Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA.International journal of molecular sciences · 2023Review
- The WID-BC-index identifies women with primary poor prognostic breast cancer based on DNA methylation in cervical samples.Nature communications · 2022Article
- Review
- Peripheral bloodJournal of gynecologic oncology · 2021Article
- Comments on: Peripheral bloodJournal of gynecologic oncology · 2021Article
- Quantitative comparison of within-sample heterogeneity scores for DNA methylation data.Nucleic acids research · 2020Article
- Non-Surgical Cancer Risk Reduction inCancers · 2020Article
- A novel fluorescent biosensor based on dendritic DNA nanostructure in combination with ligase reaction for ultrasensitive detection of DNA methylation.Journal of nanobiotechnology · 2019Article
- Integrative pathway-based survival prediction utilizing the interaction between gene expression and DNA methylation in breast cancer.BMC medical genomics · 2018Article
- DNA methylation signatures of breast cancer in peripheral T-cells.BMC cancer · 2018Article
- Epigenome-based cancer risk prediction: rationale, opportunities and challenges.Nature reviews. Clinical oncology · 2018Review
- Review
- Elucidating the Underlying Functional Mechanisms of Breast Cancer Susceptibility Through Post-GWAS Analyses.Frontiers in genetics · 2018Review
- Are objective measures of physical capability related to accelerated epigenetic age? Findings from a British birth cohort.BMJ open · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundBRCA1 mutation carriers have an 85% risk of developing breast cancer but the risk of developing non-hereditary breast cancer is difficult to assess. Our objective is to test whether a DNA methylation (DNAme) signature derived from BRCA1 mutation carriers is able to predict non-hereditary breast cancer.
methodsIn a case/control setting (72 BRCA1 mutation carriers and 72 BRCA1/2 wild type controls) blood cell DNA samples were profiled on the Illumina 27 k methylation array. Using the Elastic Net classification algorithm, a BRCA1-mutation DNAme signature was derived and tested in two cohorts: (1) The NSHD (19 breast cancers developed within 12 years after sample donation and 77 controls) and (2) the UKCTOCS trial (119 oestrogen receptor positive breast cancers developed within 5 years after sample donation and 122 controls).
resultsWe found that our blood-based BRCA1-mutation DNAme signature applied to blood cell DNA from women in the NSHD resulted in a receiver operating characteristics (ROC) area under the curve (AUC) of 0.65 (95% CI 0.51 to 0.78, P = 0.02) which did not validate in buccal cells from the same individuals. Applying the signature in blood DNA from UKCTOCS volunteers resulted in AUC of 0.57 (95% CI 0.50 to 0.64; P = 0.03) and is independent of family history or any other known risk factors. Importantly the BRCA1-mutation DNAme signature was able to predict breast cancer mortality (AUC = 0.67; 95% CI 0.51 to 0.83; P = 0.02). We also found that the 1,074 CpGs which are hypermethylated in BRCA1 mutation carriers are significantly enriched for stem cell polycomb group target genes (P <10(-20)).
conclusionsA DNAme signature derived from BRCA1 carriers is able to predict breast cancer risk and death years in advance of diagnosis. Future studies may need to focus on DNAme profiles in epithelial cells in order to reach the AUC thresholds required of preventative measures or early detection strategies.
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