ArticleClinical epigenetics2018
Increased epigenetic age in normal breast tissue from luminal breast cancer patients.
Article in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Chemical and climatic environmental exposures and epigenetic aging: A systematic review.Environmental research · 2025Pooled it
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- Associations of breast DNA methylation-based measures of biological ageing with obesity-related breast cancer risk markers.Epigenetics · 2026Article
- Can DNA Methylation in Peritumoral and Contralateral Breast Tissue Predict Recurrence or Second Breast Cancers?Current issues in molecular biology · 2026Article
- Molecular underpinnings of induced degenerative heterogeneity in the retinal pigment epithelium.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mutational landscape of normal breast tissues adjacent to invasive breast cancer.Cell reports. Medicine · 2026Article
- Decitabine Induces Subtype-Specific Epigenomic Remodeling and Perturbs Age-Associated Regulatory CpGs in Breast Cancer.Cancer informatics · 2026Article
- Mammo-AGE: deep learning estimation of breast age from mammograms.Nature communications · 2025Article
- Reprogramming cellular senescence and aging clocks for advanced cancer immunotherapy.Molecular cancer · 2025Review
- Placental epigenetic clocks derived from crowdsourcing: Implications for the study of accelerated aging in obstetrics.iScience · 2025Article
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- Network-based approach elucidates critical genes in BRCA subtypes and chemotherapy response in triple negative breast cancer.iScience · 2024Article
- A Review: Multi-Omics Approach to Studying the Association between Ionizing Radiation Effects on Biological Aging.Biology · 2024Review
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- Current status and challenges of breast cancer prevention~DNA methylation would lead to groundbreaking progress in breast cancer prevention~.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023Review
- Loss of epigenetic suppression of retrotransposons with oncogenic potential in aging mammary luminal epithelial cells.Genome research · 2023Article
- Study on promoting the regeneration of grafted fat by cell-assisted lipotransfer.Regenerative therapy · 2023Article
- Analysis of Pregnancy Complications and Epigenetic Gestational Age of Newborns.JAMA network open · 2023Article
- Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAge is one of the most important risk factors for developing breast cancer. However, age-related changes in normal breast tissue that potentially lead to breast cancer are incompletely understood. Quantifying tissue-level DNA methylation can contribute to understanding these processes. We hypothesized that occurrence of breast cancer should be associated with an acceleration of epigenetic aging in normal breast tissue.
resultsNinety-six normal breast tissue samples were obtained from 88 subjects (breast cancer = 35 subjects/40 samples, unaffected = 53 subjects/53 samples). Normal tissue samples from breast cancer patients were obtained from distant non-tumor sites of primary mastectomy specimens, while samples from unaffected women were obtained from the Komen Tissue Bank (n = 25) and from non-cancer-related breast surgery specimens (n = 28). Patients were further stratified into four cohorts: age < 50 years with and without breast cancer and age ≥ 50 with and without breast cancer. The Illumina HumanMethylation450k BeadChip microarray was used to generate methylation profiles from extracted DNA samples. Data was analyzed using the "Epigenetic Clock," a published biomarker of aging based on a defined set of 353 CpGs in the human genome. The resulting age estimate, DNA methylation age, was related to chronological age and to breast cancer status. The DNAmAge of normal breast tissue was strongly correlated with chronological age (r = 0.712, p < 0.001). Compared to unaffected peers, breast cancer patients exhibited significant age acceleration in their normal breast tissue (p = 0.002). Multivariate analysis revealed that epigenetic age acceleration in the normal breast tissue of subjects with cancer remained significant after adjusting for clinical and demographic variables. Additionally, smoking was found to be positively correlated with epigenetic aging in normal breast tissue (p = 0.012).
conclusionsWomen with luminal breast cancer exhibit significant epigenetic age acceleration in normal adjacent breast tissue, which is consistent with an analogous finding in malignant breast tissue. Smoking is also associated with epigenetic age acceleration in normal breast tissue. Further studies are needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of incident breast cancer and whether this mediates the risk of chronological age on breast cancer risk.
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