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Epidemiologic considerations to assess altered DNA methylation from environmental exposures in cancer
Lee E Moore1, Wen-Yi Huang, Joyce Chung
1Occupational Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. moorele@mail.nih.gov
Abstract:
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.
Insights
Environmental exposures can alter cancer risk by changing DNA methylation, a key epigenetic mechanism. Molecular epidemiology studies should incorporate epigenetic markers to fully understand cancer causation from these exposures.
Area of Science:
- Environmental Health
- Molecular Epidemiology
- Epigenetics
Background:
- Cancer epidemiology traditionally focuses on gene-damaging agents.
- Exogenous agents, including environmental factors, can induce epigenetic changes like DNA methylation.
- Understanding these epigenetic alterations is crucial for comprehensive cancer risk assessment.
Purpose of the Study:
- To review the impact of exogenous agents on DNA methylation.
- To discuss genes involved in susceptibility to aberrant DNA methylation and cancer development.
- To explore methods for integrating DNA methylation markers into molecular epidemiology.
Main Methods:
- Literature review of studies on exogenous agents and DNA methylation.
- Categorization of genes based on their interaction with DNA methylation patterns.
- Discussion of methodologies for incorporating epigenetic markers in etiological research.
Main Results:
- Exogenous agents (micronutrients, metals, etc.) can significantly impact DNA methylation.
- Identified two gene categories: those affecting methylation susceptibility and those silenced by methylation.
- Proposed approaches for integrating DNA methylation markers into disease etiology studies.
Conclusions:
- Epigenetic changes, particularly DNA methylation, are critical pathways linking environmental exposures to cancer.
- Incorporating epigenetic markers enhances molecular epidemiology for a deeper understanding of cancer risk factors.
- Further research integrating environmental exposures, epigenetics, and cancer etiology is warranted.