Epidemiologic Considerations to Assess Altered DNA Methylation from Environmental Exposures in Cancer

: Epidemiologic studies in human populations have identified a broad spectrum of risk factors for cancer. Gene-damaging agents have been a primary focus of cancer epidemiology; however, all xenobiotics do not interact with DNA directly. Some exogenous agents induce epigenetic changes. In view of this, markers that measure changes to the epigenome must also be incorporated into molecular epidemiologic studies. We review the current understanding of the impact of exogenous agents including: micronutrients, chemotherapeutic agents, metals, and others, on DNA methylation. Two categories of genes are described: (1) genes that can alter susceptibility to aberrant DNA methylation and (2) genes that increase susceptibility to cancer when they are silenced through DNA methylation. Methods for incorporating markers of DNA methylation status into etiologic investigations of the impact of environmental exposures on disease (e.g., cancer) are discussed.