Epigenetic signatures in surrogate tissues are able to assess cancer risk and indicate the efficacy of preventive measures

Sep 23, 2026

Epigenetic signatures in surrogate tissues can serve as accessible biomarkers for primary cancer prevention. Using a mouse model of mammary gland cancer induced by medroxyprogesterone acetate and 7,12-dimethylbenzanthracene, the study evaluates epigenetic patterns, cell-type composition, mitotic age, and methylation at progesterone receptor binding sites in both tissue at risk and distant non-at-risk organs. Treatment with the anti-progestin mifepristone reduces cancer risk by over 50%, accompanied by declines in field cancerization and field defect indicators. Cervical epigenetic signatures predict mammary cancer formation with tissue-specific directionality.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

communications medicine Article A Nature Portfolio journal [https://doi.org/10.1038/s43856-025-00779-w](https://doi.org/10.1038/s43856-025-00779-w) Epigenetic signatures in surrogatetissues are able to assess cancer risk and indicate the efﬁcacy of preventive measures Check for updates | James E. Barrett1,2,12, Chiara Maria Herzog 1,2,12, Sepideh Aminzadeh-Gohari1,2,3,12, Elisa Redl Isma Ishaq Parveen1,2, Julia Rothärmel1,2, Julia Tevini 3, Daniela D. Weber 3, Luca Catalano3, Victoria E. Stefan3,4, Thomas K. Felder 5,6, Peter Obrist7, Twana Alkasalias 8,9,
Kristina Gemzell-Danielsson 9, Roland Lang 10, Barbara Koﬂer3 & Martin Widschwendter | | | 1,2
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1,2,9,11 | | --- | --- | --- | --- | | Abstract | | Plain Language Summary | | | Background In order to advance personalized primary cancer prevention, surrogate endpoint biomarkers in distant, easy to access tissues (i.e., ﬁeld defect indicators) reﬂecting ﬁeld cancerization in the organ at risk are essential.
Methods Here we utilized medroxyprogesterone acetate and 7,12-dimethylbenzanthracene to induce mammary gland cancers in mice. We assessed epigenetic signatures reﬂective of carcinogen exposure, cell-type composition, mitotic age, and methylation at progesterone receptor binding sites in both, the tissue at risk (normal mammary gland; ﬁeld cancerization) and distant non-at-risk organs(cervix, oviduct, and blood;ﬁeld defect indicators), in mice that did and did not develop mammary gland cancers.
Results We demonstrate that the anti-progestine mifepristone reduces the cancer risk by more than50% . Importantly, the reduction incancerriskis accompanied by a decline in both ﬁeld cancerization andﬁeld defect indicators;speciﬁcally, epigenetic signatures in the cervix are predictive of mammary cancer formation but show tissue-speciﬁc directionality. Conclusions These data encourage further exploration of epigenetic biomarkers in certain ﬁeld defect-indicating tissues with a view to monitor the efﬁcacy of cancer prevention strategies in humans. | | Molecules within the body that can be used as indicators that cancer is present are called biomarkers. Ideally, they are obtained from parts of the body that are easy to access, such asthe blood, even ifthey are farfrom the actual site of cancer. Here, we used mice to model breast cancer and looked at biomarkers in the mammary gland, where cancer occurs, distant organs (including the cervix) and blood. We found that the amount of the hormone progesterone present has a role in increasing cancer risk. Mifepristone, an existing drug that blocks the effects of progesterone, reduced the risk of mammary gland cancer by over 50% . Changes in biomarkers in the cervix could be used to predict whether the mouse would develop cancer in the mammary gland, suggesting that these markers could help monitor whether cancer prevention strategies are working in humans. | | | Cancer is likelyto become the most prevalent disease and the most common cause of death in the near future1. Currently, primary cancer prevention strategies are still limited. Itiswell known that speciﬁc risk factors, including progesterone exposure, drive a phenomenon called ﬁeld cancerization, which is the replacement of the normal cell population by a cancer-primed | cell population that shows no morphological changes2. Whereas ﬁeld cancerization by deﬁnitionis limited to the organ at risk(e.g., breast3 or fallopian tube4), preliminary evidence supports the idea that ﬁeld defect indicators exist in non-at-risk organs (e.g., blood or cervical cells) distant from the tissue at risk. Therefore, ﬁeld defect-indicating biomarkers are suitable to | | | 1European Translational Oncology Prevention and Screening (EUTOPS) Institute, University Innsbruck, Hall in Tirol, Austria. 2Institute for Biomedical Aging Research, University Innsbruck, Innsbruck, Austria. 3Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Uni

FAQs

What is the main purpose of the study?

To evaluate whether epigenetic signatures in surrogate, easily accessible tissues can assess cancer risk and reflect the efficacy of preventive measures.

How was the cancer model established in the experiments?

Mammary gland cancers were induced in mice using medroxyprogesterone acetate and 7,12-dimethylbenzanthracene.

What effect did mifepristone have on cancer outcomes?

Mifepristone reduced mammary cancer risk by more than 50%, with accompanying decreases in field cancerization and field defect indicators.

Sep 23, 2026

Uploaded by Lucas Martin