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

doi:10.1016/j.ebiom.2016.02.008

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

164 Scopus citations

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 δ_age (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, δ_age 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, δ_age was associated with cancer risks in a dose-responsive manner (P = 0.02) and a one-year increase in δ_age 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 δ_age and decelerated epigenetic aging over time had the lowest risks of cancer incidence (P = 0.003) and mortality (P = 0.02). δ_age 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.

Original language	English (US)
Pages (from-to)	68-73
Number of pages	6
Journal	EBioMedicine
Volume	5
DOIs	https://doi.org/10.1016/j.ebiom.2016.02.008
State	Published - Mar 1 2016

Funding

This study was funded by the Epidemiology Research and Information Center, U.S. Department of Veterans Affairs; NIEHS R01-ES015172 . Additional funding support was provided by the Northwestern University Robert H. Lurie Comprehensive Cancer Center Rosenberg Research Fund . The funding institutions had no role in the study design, data collection or analysis, interpretation of findings, manuscript preparation, or decision to pursue peer-review publication. No author has been paid to write this article by a pharmaceutical company or other agency.

Keywords

Cancer risk
DNA methylation
Epigenetic age

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ebiom.2016.02.008

Cite this

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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.",

keywords = "Cancer risk, DNA methylation, Epigenetic age",

author = "Yinan Zheng and Joyce, {Brian T.} and Elena Colicino and Lei Liu and Wei Zhang and Qi Dai and Shrubsole, {Martha J.} and Kibbe, {Warren A.} and Tao Gao and Zhou Zhang and Nadereh Jafari and Pantel Vokonas and Joel Schwartz and Baccarelli, {Andrea A.} and Lifang Hou",

note = "Funding Information: This study was funded by the Epidemiology Research and Information Center, U.S. Department of Veterans Affairs; NIEHS R01-ES015172 . Additional funding support was provided by the Northwestern University Robert H. Lurie Comprehensive Cancer Center Rosenberg Research Fund . The funding institutions had no role in the study design, data collection or analysis, interpretation of findings, manuscript preparation, or decision to pursue peer-review publication. No author has been paid to write this article by a pharmaceutical company or other agency. Publisher Copyright: {\textcopyright} 2016 The Authors.",

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doi = "10.1016/j.ebiom.2016.02.008",

language = "English (US)",

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T1 - Blood Epigenetic Age may Predict Cancer Incidence and Mortality

AU - Zheng, Yinan

AU - Joyce, Brian T.

AU - Colicino, Elena

AU - Liu, Lei

AU - Zhang, Wei

AU - Dai, Qi

AU - Shrubsole, Martha J.

AU - Kibbe, Warren A.

AU - Gao, Tao

AU - Zhang, Zhou

AU - Jafari, Nadereh

AU - Vokonas, Pantel

AU - Schwartz, Joel

AU - Baccarelli, Andrea A.

AU - Hou, Lifang

N1 - Funding Information: This study was funded by the Epidemiology Research and Information Center, U.S. Department of Veterans Affairs; NIEHS R01-ES015172 . Additional funding support was provided by the Northwestern University Robert H. Lurie Comprehensive Cancer Center Rosenberg Research Fund . The funding institutions had no role in the study design, data collection or analysis, interpretation of findings, manuscript preparation, or decision to pursue peer-review publication. No author has been paid to write this article by a pharmaceutical company or other agency. Publisher Copyright: © 2016 The Authors.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

AB - 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.

KW - Cancer risk

KW - DNA methylation

KW - Epigenetic age

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JO - EBioMedicine

JF - EBioMedicine

ER -

Blood Epigenetic Age may Predict Cancer Incidence and Mortality

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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