TY - JOUR
T1 - Epigenetic signatures in surrogate tissues are able to assess cancer risk and indicate the efficacy of preventive measures
AU - Barrett, James E
AU - Herzog, Chiara Maria
AU - Aminzadeh-Gohari, Sepideh
AU - Redl, Elisa
AU - Ishaq Parveen, Isma
AU - Rothärmel, Julia
AU - Tevini, Julia
AU - Weber, Daniela D
AU - Catalano, Luca
AU - Stefan, Victoria E
AU - Felder, Thomas K
AU - Obrist, Peter
AU - Alkasalias, Twana
AU - Gemzell-Danielsson, Kristina
AU - Lang, Roland
AU - Kofler, Barbara
AU - Widschwendter, Martin
N1 - Aminzadeh-Gohar, Tevini, Weber, Catalano, Stefan, Kofler:Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical University, Salzburg, Austria; Felder: Department of Laboratory Medicine, University Hospital of the Paracelsus Medical University, Salzburg, Austria; Institute of Pharmacy, Paracelsus Medical
University, Salzburg, Austria; Lang: Department of
Dermatology and Allergology, University Hospital of the Paracelsus Medical University, Salzburg, Austria.
PY - 2025/4/2
Y1 - 2025/4/2
N2 - 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 than 50%. Importantly, the reduction in cancer risk is accompanied by a decline in both field cancerization and field 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.
AB - 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 than 50%. Importantly, the reduction in cancer risk is accompanied by a decline in both field cancerization and field 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.
U2 - 10.1038/s43856-025-00779-w
DO - 10.1038/s43856-025-00779-w
M3 - Original Article
C2 - 40175633
SN - 2730-664X
VL - 5
SP - 97
JO - COMMUNICATIONS MEDICINE
JF - COMMUNICATIONS MEDICINE
IS - 1
M1 - 97
ER -