Blood Epigenetic Age may Predict Cancer Incidence and Mortality

• We prospectively examined blood Δage and its ability to predict cancer risks.
• Epigenetic age older than chronological age elevated cancer risk.
• Δage predicted cancer incidence and mortality in a dose-responsive manner.
• The Δage–cancer relationship was a nonlinear ‘J-shape’ for subjects measured before 2003.Blood-based epigenetic age is a potential biomarker for cancer early detection.This study studies a way to calculate your body's age, not based on how old you are, but by measuring a number of markers in your blood — called epigenetic age. This paper also looks at how good epigenetic age over time is at predicting whether you'll get cancer, and whether you'll die from it. The authors found that epigenetic age could be good at predicting both of these things, which means that someday it could be developed into a blood test for diagnosing cancer, and for helping patients figure out how long they'll live.

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.