title: Blood Epigenetic Age may Predict Cancer Incidence and Mortality.
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.
authors.affiliation: 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.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Joyce
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Colicino
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Dai
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Shrubsole
authors.affiliation: 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.
authors.forename: Warren A
authors.initials: WA
authors.lastname: Kibbe
authors.affiliation: Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Genomics Core Facility, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Nadereh
authors.initials: N
authors.lastname: Jafari
authors.affiliation: VA Boston Healthcare System and Boston University Schools of Public Health and Medicine, Boston, MA 02215, USA.
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.affiliation: 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.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: 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.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D057890:Epigenomics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology
keywords: Cancer risk; DNA methylation; Epigenetic age