Research Paper Advance Articles
DNA-methylation age and accelerated epigenetic aging in blood as a tumor marker for predicting breast cancer susceptibility
- 1 Translational Sciences Section, School of Nursing, University of California, Los Angeles, CA 90095, USA
- 2 Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA 90095, USA
- 3 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA
- 4 Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA
- 5 Department of Quantitative Health Sciences, Bioinformatics Core, John A. Burns School of Medicine, University of Hawaii Cancer Center, Honolulu, HI 96813, USA
- 6 Department of Molecular, Cell and Developmental Biology, Life Sciences Division, University of California, Los Angeles, CA 90095, USA
Received: March 13, 2024 Accepted: November 4, 2024 Published: December 5, 2024
https://doi.org/10.18632/aging.206169How to Cite
Copyright: © 2024 Jung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: DNA methylation (DNAm)–based marker of aging, referred to as ‘epigenetic age’ or ‘DNAm age’ is a highly accurate multi-tissue biomarker for aging, associated with age-related disease risk, including cancer. Breast cancer (BC), an age-associated disease, is associated with older DNAm age and epigenetic age acceleration (age accel) at tissue levels. But this raises a question on the predictability of DNAm age/age accel in BC development, emphasizing the importance of studying DNAm age in pre-diagnostic peripheral blood (PB) in BC etiology and prevention.
Methods: We included postmenopausal women from the largest study cohort and prospectively investigated BC development with their pre-diagnostic DNAm in PB leukocytes (PBLs). We estimated Horvath’s pan-tissue DNAm age and investigated whether DNAm age/age accel highly correlates with risk for developing subtype-specific BC and to what degree the risk is modified by hormones and lifestyle factors.
Results: DNAm age in PBLs was tightly correlated with age in this age range, and older DNAm age and epigenetic age accel were significantly associated with risk for developing overall BC and luminal subtypes. Of note, in women with bilateral oophorectomy before natural menopause experiencing shorter lifetime estrogen exposure than those with natural menopause, epigenetic age accel substantially influenced BC development, independent of obesity status and exogeneous estrogen use.
Conclusions: Our findings contribute to better understanding of biologic aging processes that mediate BC carcinogenesis, detecting a non-invasive epigenetic aging marker that better reflects BC development, and ultimately identifying the elderly with high risk who can benefit from epigenetically targeted preventive interventions.