The Epithelial Epigenome: A Unified Platform for Cancer Risk Prediction and Prevention Monitoring

Intrinsic biological processes and carcinogenic exposures leave cumulative DNA methylation (DNAme) imprints in epithelial cells. These changes reflect cellular composition, replicative/mitotic age and impaired differentiation capacity, and arise long before clinically detectable cancer, consistent with the concept of field cancerisation. Importantly, such epigenetic alterations are not confined to the tissue of origin but extend to anatomically distant epithelia that share developmental lineage and/or carcinogen exposure/susceptibility, thereby serving as field defect indicators. Notably, these signatures are dynamic and responsive to preventive interventions, enabling both risk assessment and real-time monitoring of prevention efficacy. The epithelial epigenome is thus emerging as a unified, minimally invasive platform for personalised, multi-cancer prevention.