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DNA Methylation and Smoking: Implications for Understanding Effects of Electronic Cigarettes

  • Cancer Epidemiology (MB Terry, Section Editor)
  • Published:
Current Epidemiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Use of electronic cigarettes (e-cigs) has increased sharply recently although understanding of toxicity is limited, particularly target organ effects. Altered DNA methylation is a reversible response to environmental exposures, including smoking, and may be useful as a biomarker of e-cig harm.

Recent Findings

Among studies examining DNA methylation in blood by smoking status, there is considerable variability in differentially methylated CpGs identified; certain CpGs are consistently found. These include AHRR (aryl hydrocarbon receptor repressor gene), particularly cg05575921, cg0363183 in the F2RL2 gene coding for the protease-activated receptor 4 (PAR-4), and several CpGs in the 2q37.1 genomic region. Differences are found even with short duration and light smoking; effects vary with pack-years and time since quitting among former smokers. For tissues other than blood, data are limited but also indicate altered methylation with smoking.

Summary

DNA methylation changes are a consistent biomarker of smoke exposure. Most studies regarding smoke effects on methylation are of blood cells; further evidence regarding effects of smoke, secondhand smoke, and e-cigs on target tissues for smoking-related diseases are needed. Understanding biological effects of e-cigs is critically important to inform regulation; examination of e-cig effects on DNA methylation can significantly add to evidence-based regulation.

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Funding

Supported in part by funding from the Prevent Cancer Foundation, the National Cancer Institute of the National Institutes of Health (NIH) (P50CA180908 and UL1TR001070), the Food and Drug Administration (FDA) Center for Tobacco Products (P30 CA016058), and the National Center for Advancing Translational Sciences.

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Authors and Affiliations

  1. Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, 270 Farber Hall, Buffalo, NY, 14214, USA

    Jo L. Freudenheim

  2. Comprehensive Cancer Center, The Ohio State University and James Cancer Hospital, Columbus, OH, USA

    Peter G. Shields & Min-Ae Song

  3. Division of Environmental Health Science, College of Public Health, The Ohio State University, Columbus, OH, USA

    Min-Ae Song

  4. Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Dominic Smiraglia

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  1. Jo L. Freudenheim
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  4. Dominic Smiraglia
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Corresponding author

Correspondence to Jo L. Freudenheim.

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The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the FDA.

Conflict of Interest

Jo L. Freudenheim reports grants from Prevent Cancer Foundation, during the conduct of the study.

Peter G Shields reports grants from NCI - Models for Tobacco Product Evaluation, grants from NCI -Multi-investigator grant investigating the use of multiple tobacco projects in adolescents and adults, grants from NIDA - The Effects of a Standardized Research E-Cigarette On The Human Lung: A Clinical Trial With Bronchoscopic Biomarkers, and grants from OSUCCC A Pilot Study Assessing Electronic Cigarette and Tobacco Product Lung Toxicity, during the conduct of the study. Also, Dr. Shields serves as an expert witness in tobacco litigation cases. Min-Ae Song and Dominic Smiraglia each declare no potential conflicts of interest.

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Freudenheim, J.L., Shields, P.G., Song, MA. et al. DNA Methylation and Smoking: Implications for Understanding Effects of Electronic Cigarettes. Curr Epidemiol Rep 6, 148–161 (2019). https://doi.org/10.1007/s40471-019-00191-8

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