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Biological aging measures based on blood DNA methylation and risk of cancer: a prospective study

By Pierre-Antoine Dugue, Julie K Bassett, Ee Ming Wong, JiHoon E Joo, Shuai Li, Chenglong Yu, Daniel F Schmidt, Enes Makalic, Nicole Wong Doo, Daniel D Buchanan, Allison M Hodge, Dallas R English, John L Hopper, Graham G Giles, Melissa C Southey, Roger L. Milne

Posted 11 Apr 2020
medRxiv DOI: 10.1101/2020.04.08.20058727

BackgroundWe previously investigated the association between five first-generation measures of epigenetic aging and cancer risk in the Melbourne Collaborative Cohort Study. The present study assessed cancer risk associations for three recently developed methylation-based biomarkers of aging: PhenoAge, GrimAge, and predicted telomere length. MethodsWe estimated rate ratios (RRs) for the association between these three age-adjusted measures and risk of colorectal (N=813), gastric (N=165), kidney (N=139), lung (N=327), mature B-cell (N=423), prostate (N=846) and urothelial (N=404) cancer, using conditional logistic regression models. We also assessed associations by time since blood draw and by cancer subtype, and investigated potential non-linearity. ResultsWe observed relatively strong associations of age-adjusted PhenoAge with risk of colorectal, kidney, lung, mature B-cell, and urothelial cancers (RR per standard deviation [SD][~]1.2-1.3). Similar findings were obtained for age-adjusted GrimAge, but the association with lung cancer risk was much larger, RR per SD=1.82, 95%CI=1.44-2.30, after adjustment for smoking status, pack-years, starting age, time since quitting and other cancer risk factors. Most associations appeared linear, larger than for the first-generation measures, and were virtually unchanged after adjustment for a large set of sociodemographic, lifestyle and anthropometric variables. For cancer overall, the comprehensively-adjusted RR per SD was 1.13, 95%CI=1.07-1.19, for PhenoAge and 1.12, 95%CI=1.05-1.20, for GrimAge, and appeared larger within 5 years of blood draw (RR=1.29 and 1.19, respectively). ConclusionThe methylation-based measures PhenoAge and GrimAge may provide insights into the relationship between biological aging and cancer and be useful to predict cancer risk, particularly for lung cancer.

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