Epigenetic mechanisms and cancer: an interface between the environment and the genome.

Although epidemiological studies support the role of environment in a wide range of human cancers, the precise mechanisms by which environmental exposures promote cancer development and progression remain poorly understood. Environmental factors have been proposed to promote the development of malignancies by eliciting epigenetic changes; however, it is only with recent advances in epigenetics and epigenomics that target genes and the mechanisms underlying environmental influences are beginning to be elucidated. Because epigenetic mechanisms may function as an interface between environmental factors and the genome, deregulation of the epigenome by environmental stressors is likely to disrupt different cellular processes and contribute to cancer risk. In addition, the early appearance and ubiquity of epigenetic changes in virtually all steps of tumor development and progression in most, if not all, human neoplasms, make them attractive targets for biomarker discovery and targeted prevention. At the cellular level, aberrant epigenetic changes associated with environmental exposures may deregulate key cellular processes (including transcriptional control, DNA repair, cell cycle control, and carcinogen detoxification), which can be further modulated by environmental stressors, thus defining not only the phenotype of the disease but also potential biomarkers. This review summarizes recent progress in our understanding of the epigenetic mechanisms through which environmental factors may promote tumor development, with a particular focus on human lung cancer.