Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois-Chicago, Chicago, IL 60613, USA.
EBioMedicine. 2016 Feb 8;5:68-73. doi: 10.1016/j.ebiom.2016.02.008. eCollection 2016 Mar.
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.
生物衰老指标对于了解老龄化人口的健康状况非常重要，其中表观遗传学尤其有前景。先前的研究发现，肿瘤组织在表观遗传学上比其供体的年龄大。我们研究了血液Δ年龄（表观年龄与实际年龄之间的差异）是否可以预测癌症的发病率或死亡率，从而评估其作为癌症生物标志物的潜力。在一项前瞻性队列研究中，我们在 442 名在采血时无癌症的参与者的 834 个白细胞样本中计算了Δ年龄及其随时间的变化率。在癌症发病或死亡前约 3-5 年，Δ年龄与癌症风险呈剂量反应关系（P=0.02），Δ年龄增加一年与癌症发病率（HR：1.06，95%CI：1.02-1.10）和死亡率（HR：1.17，95%CI：1.07-1.28）相关。Δ年龄较小且表观遗传学衰老随时间减速的参与者的癌症发病率（P=0.003）和死亡率（P=0.02）最低。对于在 2003 年之前接受检查的受试者，Δ年龄与癌症发病率呈“J 形”相关，而与癌症死亡率呈时变相关。我们得出结论，血液表观遗传学年龄可能反映与癌症发展相关的表观遗传异常，可能成为癌症早期检测的微创生物标志物。
