Epigenetic aging and cancer incidence in a German cohort of older adults

Rising life expectancy and an aging population highlight the importance of cancer control. DNA methylation (DNAm)-based biological age (BA) may provide insights into aging, carcinogenesis, and cancer prevention and care. We estimated five BA metrics among 1916 participants aged 50-75 years at baseline in the German ESTHER cohort, with repeat BA measurements available for 894 participants after 8 years. Multivariable linear regression was used to assess associations between prior cancer and baseline BA, while Cox proportional hazards models and restricted cubic splines evaluated associations of BA levels and trajectories with subsequent cancer risk. A history of malignant tumors was associated with higher baseline PCHannum and PCGrimAge in fully adjusted models. Older BA levels were significantly associated with increased long-term cancer risk, with hazard ratios up to 1.67 (95% CI 1.25-2.24) per standard deviation (SD) increase in PCGrimAge. Except for PCGrimAge, BA trajectories showed monotonic, linear associations with cancer risk, corresponding to a 33% to 37% higher risk per SD increase in slopes of four BA matrices. Accelerated biological aging was consistently associated with increased overall cancer risk, highlighting the potential value of longitudinal BA measures for cancer risk assessment, prevention, and monitoring.