Blood Epigenetic Age may Predict Cancer Incidence and Mortality
Yinan Zheng,
Brian T. Joyce,
Elena Colicino,
Lei Liu,
Wei Zhang,
Qi Dai,
Martha J. Shrubsole,
Warren A. Kibbe,
Tao Gao,
Zhou Zhang,
Nadereh Jafari,
Pantel Vokonas,
Joel Schwartz,
Andrea A. Baccarelli,
Lifang Hou
Affiliations
Yinan Zheng
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Brian T. Joyce
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Elena Colicino
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Lei Liu
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Wei Zhang
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Qi Dai
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA
Martha J. Shrubsole
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA
Warren A. Kibbe
Center for Biomedical Informatics and Information Technology, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850, USA
Tao Gao
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Zhou Zhang
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Nadereh Jafari
Genomics Core Facility, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Pantel Vokonas
VA Boston Healthcare System and Boston University Schools of Public Health and Medicine, Boston, MA 02215, USA
Joel Schwartz
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Andrea A. Baccarelli
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
Lifang Hou
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
Biological measures of aging are important for understanding the health of an aging population, with epigenetics particularly promising. Previous studies found that tumor tissue is epigenetically older than its donors are chronologically. We examined whether blood Δage (the discrepancy between epigenetic and chronological ages) can predict cancer incidence or mortality, thus assessing its potential as a cancer biomarker. In a prospective cohort, Δage and its rate of change over time were calculated in 834 blood leukocyte samples collected from 442 participants free of cancer at blood draw. About 3–5 years before cancer onset or death, Δage was associated with cancer risks in a dose-responsive manner (P = 0.02) and a one-year increase in Δage was associated with cancer incidence (HR: 1.06, 95% CI: 1.02–1.10) and mortality (HR: 1.17, 95% CI: 1.07–1.28). Participants with smaller Δage and decelerated epigenetic aging over time had the lowest risks of cancer incidence (P = 0.003) and mortality (P = 0.02). Δage was associated with cancer incidence in a ‘J-shaped’ manner for subjects examined pre-2003, and with cancer mortality in a time-varying manner. We conclude that blood epigenetic age may mirror epigenetic abnormalities related to cancer development, potentially serving as a minimally invasive biomarker for cancer early detection.
