Blood Epigenetic Age may Predict Cancer Incidence and Mortality

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.