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

73 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

Keywords

Cancer risk
DNA methylation
Epigenetic age

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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@article{8b3531ac1adc42ed8dc9f9f2276b9a7d,

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 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. ",

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. ",

year = "2016",

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day = "1",

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

language = "English (US)",

volume = "5",

pages = "68--73",

journal = "EBioMedicine",

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Blood Epigenetic Age may Predict Cancer Incidence and Mortality. / Zheng, Yinan ; Joyce, Brian T.; Colicino, Elena; Liu, Lei; Zhang, Wei; Dai, Qi; Shrubsole, Martha J.; Kibbe, Warren A.; Gao, Tao; Zhang, Zhou; Jafari, Nadereh; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A.; Hou, Lifang.

In: EBioMedicine, Vol. 5, 01.03.2016, p. 68-73.

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

TY - JOUR

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.

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 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.

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 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.

KW - Cancer risk

KW - DNA methylation

KW - Epigenetic age

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