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EBioMedicine. 2016 Feb 8;5:68-73. doi: 10.1016/j.ebiom.2016.02.008. eCollection 2016 Mar.

Blood Epigenetic Age may Predict Cancer Incidence and Mortality.

Author information

1
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
2
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois-Chicago, Chicago, IL 60613, USA.
3
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
4
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
5
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
6
Center for Biomedical Informatics and Information Technology, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850, USA; Biomedical Informatics Center (NUBIC), Northwestern University Clinical and Translational Sciences Institute (NUCATS), Chicago, IL 60611, USA.
7
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
8
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Driskill Graduate Program in Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
9
Genomics Core Facility, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
10
VA Boston Healthcare System and Boston University Schools of Public Health and Medicine, Boston, MA 02215, USA.
11
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.

Abstract

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.

KEYWORDS:

Cancer risk; DNA methylation; Epigenetic age

PMID:
27077113
PMCID:
PMC4816845
DOI:
10.1016/j.ebiom.2016.02.008
[Indexed for MEDLINE]
Free PMC Article

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