ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2021
The Effects of Lifetime Estrogen Exposure on Breast Epigenetic Age.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 30 citations in OpenAlex.
- Association of cumulative lifetime estrogen exposure and reproductive factors with breast cancer molecular subtype among Nigerian women in the MEND study.Breast cancer research and treatment · 2026Article
- Little women: the relevance and reliance on mouse models for mammary gland research and next steps for translation.Journal of mammary gland biology and neoplasia · 2025Review
- Environmental endocrine disruptors: rethinking the origins of early-onset ERNature reviews. Cancer · 2025Article
- DNA methylation patterns in breast cancer, paired benign tissue from ipsilateral and contralateral breast, and healthy controls.Breast cancer research : BCR · 2025Article
- Epigenetic ageing clocks: statistical methods and emerging computational challenges.Nature reviews. Genetics · 2025Review
- Breast Cancer risk in patients with dopamine agonist-treated hyperprolactinemia.Journal of endocrinological investigation · 2025Article
- Article
- Effect of women's fertility and sexual development on epigenetic clock: Mendelian randomization study.Clinical epigenetics · 2023Article
- Application of SHAP for Explainable Machine Learning on Age-Based Subgrouping Mammography Questionnaire Data for Positive Mammography Prediction and Risk Factor Identification.Healthcare (Basel, Switzerland) · 2023Article
- DNA methylation age in paired tumor and adjacent normal breast tissue in Chinese women with breast cancer.Clinical epigenetics · 2023Article
- The impact of reproductive factors on DNA methylation-based telomere length in healthy breast tissue.NPJ breast cancer · 2022Article
- DNA Methylation, Aging, and Cancer Risk: A Mini-Review.Frontiers in bioinformatics · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEstrogens are thought to contribute to breast cancer risk through cell cycling and accelerated breast aging. We hypothesize that lifetime estrogen exposure drives early epigenetic breast aging observed in healthy women. In this study, we examined associations between hormonal factors and epigenetic aging measures in healthy breast tissues.
methodsWe extracted DNA from breast tissue specimens from 192 healthy female donors to the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center. Methylation experiments were performed using the Illumina EPIC 850K array platform. Age-adjusted regression models were used to examine for associations between factors related to estrogen exposure and five DNA methylation-based estimates: Grim age, pan-tissue age, Hannum age, phenotypic age, and skin and blood clock age.
resultsWomen were aged 19-90 years, with 95 premenopausal, and 97 nulliparous women. The age difference (Grim age - chronologic age) was higher at earlier ages close to menarche. We found significant associations between earlier age at menarche and age-adjusted accelerations according to the Grim clock, the skin and blood clock, and between higher body mass index (BMI) and age-adjusted accelerations in the Grim clock, Hannum clock, phenotypic clock, and skin and blood clock.
conclusionsEarlier age at menarche and higher BMI are associated with elevations in DNA methylation-based age estimates in healthy breast tissues, suggesting that cumulative estrogen exposure drives breast epigenetic aging. IMPACT: Epigenetic clock measures may help advance inquiry into the relationship between accelerated breast tissue aging and an elevated incidence of breast cancer in younger women.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.