Epigenetic mechanisms are now established as the key contributors to cancer development and progression as well as to cancer phenotype. Epigenome changes, with their ubiquitous presence and great potential for modulation, have become a major focus in mechanistic studies and biomarker discovery, and in epigenetics-based cancer therapy. A plethora of recent studies has also highlighted the important role of epigenome deregulation in mediating gene–environment interactions and their effects throughout the tumorigenesis process.
This is supported by growing evidence showing that epigenetic changes may be risk factor-specific (“fingerprints”), which should prove instrumental in the discovery of new biomarkers in cancer. This progress has been catalysed by advances in epigenomics, including the emergence of powerful technologies and state-of-the-art in vitro as well as in silico computational approaches. Well-established risk factors for cancer, such as diet, tobacco smoking, alcohol consumption, fungal toxins, biological agents, and age, have been studied in the context of epigenome deregulation, along with some less widely studied exposures and lifestyle factors, such as air and water pollution and endocrine disrupters. In recent years, many international cohorts and consortia have been established, which together with sequencing technologies have galvanized investigations of epigenetic precursors of cancer and biomarkers of risk in the context of large-scale molecular epidemiology studies, including those aimed at functional characterization of the mechanistically important (driver) genes. The intrinsic reversibility of epigenetic alterations raises the prospect of the development of novel therapeutic and preventive (chemoprevention) strategies.
Despite remarkable progress in the field, there are major gaps in the understanding of the “normal” (reference) epigenome, its normal physiological variability, and specific epigenome changes associated with adverse environmental exposures and lifestyles. Major international sequencing efforts have generated a wealth of information related to the tissue- and cell type-specific epigenome (against which carcinogen exposure can be assessed) and comprehensive catalogues of epigenetic alterations across cancer types. However, a wide range of known and suspected carcinogens (including chemical, physical, and biological agents) and categories beyond environmental exposures (such as lifestyle, obesity, metabolic disorders, and physical inactivity), which are also suspected to deregulate the epigenome, are less widely studied in the context of epigenetic deregulation related to cancer causation.