Epigenetic markers of ageing and cancer risk

Epigenetic alterations are an important shared hallmark of ageing and cancer. The development of epigenetic markers of ageing using blood DNA methylation data has been an active area of research. These markers have been used to assess disease risk, with potential to shed light on the complex link between ageing and cancer. We comprehensively summarised the literature on the most widely used and recently developed epigenetic markers of ageing, and synthesised the findings from studies that assessed their associations with cancer risk. Using data from eight cancer case-control studies (Ncases = 3624) nested in the Melbourne Collaborative Cohort Study, we assessed and compared associations of these epigenetic ageing markers with cancer risk (including breast, colorectal, gastric, kidney, lung, blood, prostate, and urothelial cancers). While cancer is generally considered an ageing-related disease, the combined evidence suggested that epigenetic markers of ageing, including the most recently developed, showed generally weak associations with cancer risk and heterogeneous across markers and cancer types. The strongest associations were for lung cancer with GrimAge and its derivatives. Some associations, particularly those between mitotic clocks / stochastic epigenetic mutations and risk of blood cancer, were largely explained by underlying immune cell type heterogeneity, which was more prominent using finer cell type deconvolution. These findings indicate the potential for blood DNA methylation to help uncover the complex link between ageing and cancer and the need for new ageing markers to capture additional ageing features to improve disease risk prediction.