Abstract 4480: Blood epigenetic age may predict cancer incidence and mortality

Abstract

Abstract Biological measures of aging are important for understanding age-related cancers as the population ages. Since the epigenome is closely related to aging, epigenetics may help predict these and other age-related diseases. We aimed to prospectively examine whether blood Δage (the discrepancy between epigenetic and chronological age) can predict cancer incidence/mortality. In a prospective cohort (the Normative Aging Study), Δage and its rate of change over time were calculated using Illumina Human Methylation 450K array data in 834 blood leukocyte samples longitudinally collected from 442 participants free of cancer at the blood draw. About 3-5 years before cancer onset or death, Δage was associated with cancer risks in a dose-responsive manner (test for trend P = 0.02) and time-dependent Cox models showed a one-year increase in Δage was associated with all-cancer incidence (HR (hazard ratio): 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 (log-rank P = 0.003) and mortality (log-rank P = 0.02). Spline analysis suggested Δage was associated with cancer incidence in a ‘J-shaped’ manner, and with cancer mortality in a time-varying manner. We conclude that blood epigenetic age may mirror epigenetic abnormalities related to cancer early development or the immune response to it. Those with older epigenetic age relative to their chronological age have an elevated risk of cancer events within 3-5 years. Thus, epigenetic age could potentially serve as a novel, minimally invasive biomarker for cancer prediction. Citation Format: 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, Joel Schwartz, Andrea A. Baccarelli, Lifang Hou. Blood epigenetic age may predict cancer incidence and mortality. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4480.