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Sehl ME, Henry JE, Storniolo AM, et al. The Effects of Lifetime Estrogen Exposure on Breast Epigenetic Age. Cancer Epidemiol Biomarkers Prev. 2021;30(6):1241-1249doi: 10.1158/1055-9965.EPI-20-1297.
Sehl, M. E., Henry, J. E., Storniolo, A. M., Horvath, S., & Ganz, P. A. (2021). The Effects of Lifetime Estrogen Exposure on Breast Epigenetic Age. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 30(6), 1241-1249. https://doi.org/10.1158/1055-9965.EPI-20-1297
Sehl, Mary E, et al. "The Effects of Lifetime Estrogen Exposure on Breast Epigenetic Age." Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology vol. 30,6 (2021): 1241-1249. doi: https://doi.org/10.1158/1055-9965.EPI-20-1297
Sehl ME, Henry JE, Storniolo AM, Horvath S, Ganz PA. The Effects of Lifetime Estrogen Exposure on Breast Epigenetic Age. Cancer Epidemiol Biomarkers Prev. 2021 Jun;30(6):1241-1249. doi: 10.1158/1055-9965.EPI-20-1297. Epub 2021 Mar 26. PMID: 33771849; PMCID: PMC8172523.
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Cancer Epidemiol Biomarkers Prev. 2021 Jun;30(6):1241-1249. doi: 10.1158/1055-9965.EPI-20-1297. Epub 2021 Mar 26.

The Effects of Lifetime Estrogen Exposure on Breast Epigenetic Age.

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

Mary E Sehl, Jill E Henry, Anna M Storniolo, Steve Horvath, Patricia A Ganz

Affiliations

  1. Medicine, Hematology-Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California. [email protected].
  2. Computational Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
  3. Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center, Indianapolis, Indiana.
  4. Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, California.
  5. Department of Human Genetics, David Geffen School of Medicine, Gonda Research Center, University of California Los Angeles, California.
  6. Medicine, Hematology-Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
  7. Health Policy and Management, Fielding School of Public Health, University of California Los Angeles, California.

PMID: 33771849 PMCID: PMC8172523 DOI: 10.1158/1055-9965.EPI-20-1297

Abstract

BACKGROUND: Estrogens 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.

METHODS: We 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.

RESULTS: Women 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.

CONCLUSIONS: Earlier 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.

©2021 American Association for Cancer Research.

References

  1. Breast Cancer Res. 2018 Nov 3;20(1):132 - PubMed
  2. Aging (Albany NY). 2018 Apr 18;10(4):573-591 - PubMed
  3. Int J Mol Sci. 2019 Aug 31;20(17): - PubMed
  4. Mol Cell. 2013 Jan 24;49(2):359-367 - PubMed
  5. Front Cell Dev Biol. 2019 Aug 28;7:174 - PubMed
  6. J Natl Cancer Inst Monogr. 1994;(16):139-47 - PubMed
  7. Elife. 2020 Feb 11;9: - PubMed
  8. Epidemiol Rev. 1993;15(1):17-35 - PubMed
  9. Mol Psychiatry. 2019 Dec 3;: - PubMed
  10. Breast Cancer Res Treat. 2017 Jul;164(1):209-219 - PubMed
  11. Sci Rep. 2019 Oct 18;9(1):14991 - PubMed
  12. Aging (Albany NY). 2018 Jul 26;10(7):1758-1775 - PubMed
  13. Genome Biol. 2013;14(10):R115 - PubMed
  14. J Natl Cancer Inst. 1985 Apr;74(4):741-5 - PubMed
  15. Epigenetics. 2018;13(1):85-94 - PubMed
  16. Nat Rev Genet. 2018 Jun;19(6):371-384 - PubMed
  17. Cancer Causes Control. 1991 Jul;2(4):221-5 - PubMed
  18. Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15538-43 - PubMed
  19. Aging Cell. 2016 Feb;15(1):149-54 - PubMed
  20. Am J Epidemiol. 1988 Nov;128(5):962-79 - PubMed
  21. Breast Cancer Res Treat. 1993 Nov;28(2):179-93 - PubMed
  22. PLoS One. 2015 Mar 25;10(3):e0119201 - PubMed
  23. Clin Epigenetics. 2019 Apr 30;11(1):66 - PubMed
  24. Nucleic Acids Res. 2013 Apr;41(7):e90 - PubMed
  25. Aging (Albany NY). 2017 Feb 14;9(2):419-446 - PubMed
  26. Int J Cancer. 2020 Jul 15;147(2):375-382 - PubMed
  27. Genome Biol. 2015 Jan 30;16:25 - PubMed
  28. Aging (Albany NY). 2016 Sep 28;8(9):1844-1865 - PubMed
  29. Aging (Albany NY). 2019 Jan 21;11(2):303-327 - PubMed
  30. Nature. 1983 Jun 30;303(5920):767-70 - PubMed
  31. Clin Epigenetics. 2018 Aug 29;10(1):112 - PubMed
  32. Bioinformatics. 2017 Feb 15;33(4):558-560 - PubMed

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