Cancer epigenetics: unraveling etiology and mechanisms to advance prevention

The increased understanding of epigenetics has significantly advanced our understanding of cancer development, especially regarding environmental, occupational, and lifestyle exposures. Unlike genetic mutations, epigenetic changes may be reversible, making them critical mediators and promising targets for cancer prevention and control. This review synthesizes two decades of transformative research by the International Agency for Research on Cancer (IARC), which positioned the epigenome as a central focus in cancer epidemiology and mechanistic research among the 10 Key Characteristics (KCs) of carcinogens by the IARC Monographs program. From foundational in vitro and animal studies to large-scale population-based research, IARC researchers contributed to unraveling epigenetic mechanisms of carcinogenesis and identifying epigenetic biomarkers of exposures and cancer risk. We highlight progress in epigenetic biomarker development, mechanistic epigenomics, toxico-epigenomics, and the interplay between diet, microbiome, and epigenome. As IARC marks its 60th anniversary, this review underscores the growing role of epigenetics in guiding global cancer prevention efforts and public health strategies.