Q&A: DNA changes in vapers call for reconsideration of safeness of e-cigarettes

Key takeaways:

• There is a lack of research on how vaping changes DNA methylation.
• A recent study observed some parallels between vapers and smokers in differentially methylated region-associated genes.

The impact vaping has on DNA is just as dangerous as smoking, with both users presenting with DNA changes associated with cancer development, according to a Keck School of Medicine of University of Southern California press release.

This finding, along with others evaluating how DNA is altered in young vapers, smokers and nonusers, was published in the American Journal of Respiratory Cell and Molecular Biology.

Two researchers behind this study previously found that exclusive smokers and exclusive vapers had comparable increases in DNA damage of their oral epithelial cells.

Healio spoke with two members of the Keck School of Medicine’s department of research population and public health sciences, associate professor Stella Tommasi, PhD, and professor Ahmad Besaratinia, PhD, to learn more about their recent research and the significance of the DNA changes found in vapers and smokers.

Healio: Why are studies evaluating the oral cell methylome and epigenetic changes of vapers needed? Why did you focus specifically on young vapers/smokers/nonusers?

Tommasi and Besaratinia: The ongoing epidemic of youth vaping in the U.S. and the widespread use of e-cigarettes by adolescents and young adults (never-smokers) in many parts of the world are significant and evolving public health problems.

According to the 2023 Annual National Youth Tobacco Survey, 10% of U.S. secondary school students currently use e-cigarettes; of these, nine out of 10 use flavored e-cigarettes. To date, however, the long-term health effects of vaping are largely unknown.

Many toxicants and carcinogens present in e-cigarette vapor and cigarette smoke are known to exert their biological effects by altering the patterns of DNA methylation, a chemical modification to the DNA that affects gene expression by turning genes “on” or “off.” DNA methylation is essential for normal development and plays a crucial role in many biological processes. When dysregulated, it can contribute to the development of cancer and other diseases.

Whereas aberrant DNA methylation has been thoroughly investigated in cells and tissues of smokers, studies reporting the effects of vaping on the methylome are missing. This is the first study to profile the DNA methylation, genome-wide, in the oral epithelium of young exclusive vapers and smokers, in comparison to nonusers (nonvapers nonsmokers). We focused on youth and young adults who are a vulnerable population of special interest for tobacco product use.

The oral epithelium is the first site of direct exposure to toxicants and carcinogens present in e-cigarette vapor and cigarette smoke and a major target cell type for cancer and other diseases associated with tobacco product use. Thus, the oral epithelium represents an ideal cell type for investigating changes in DNA methylation in relation to disease risk in vapers vs. smokers.

Healio: What are differentially methylated regions? Why does the number of these regions differ between vapers, smokers and nonusers?

Tommasi and Besaratinia: Differentially methylated regions (DMRs) are areas on the genome where changes in DNA methylation occur; these regions can become more or less methylated in one group compared with other group(s) (eg, vapers vs. nonusers and smokers vs. nonusers).

DMRs generally encompass functional domains that control gene expression, thus any change in DNA methylation at these sites may lead to detrimental effects on normal cell functions.

In our study, we identified 831 DMRs in vapers and 2,863 DMRs in smokers relative to nonusers. The different number of DMRs observed in vapers and smokers likely reflects differences in source of exposure (e-cigarettes vs. tobacco cigarettes), exposure dose (intensity and duration of vaping vs. smoking) and chemical composition of the used tobacco products (types and concentrations of chemicals present in e-cigarette aerosol vs. cigarette smoke).

Healio: Based on your findings, what DMR-associated genes do vapers and smokers share? What do these genes put them at risk for?

Tommasi and Besaratinia: Vapers and smokers share 346 DMR-associated genes, which represent nearly half (46%) of the total number of DMR-associated genes detected in vapers, suggesting that vaping is likely to elicit changes in DNA methylation that are similar to those caused by smoking.

Common DMR-associated genes include genes that are known to regulate important biological signaling pathways. Dysregulation of these genes by aberrant DNA methylation can increase the risk for cancer, inflammation and other anomalies associated with tobacco use in vapers, similarly to smokers.

It is also important to note that the majority of DMR-associated genes in vapers were unique and not detectable in smokers. This is consistent with the fact that e-cigarettes produce a wide range of harmful or potentially harmful chemicals, some of which are common to those found in cigarette smoke, and some that are specific to e-cigarette vapor. Thus, clinging to a “sole” argument that e-cigarette vapor contains fewer and lower concentrations of toxic and carcinogenic compounds than cigarette smoke would be oversimplistic, and less-than adequate when assessing the health risks or potential benefits of vaping relative to smoking.

Healio: Healio previously reported on a study that found exclusive smokers and exclusive vapers had comparable increases in DNA damage of their oral epithelial cells. How does this study expand/add to this finding?

Tommasi and Besaratinia: The disease-causing effects of many toxicants and carcinogens present in both e-cigarette vapor and cigarette smoke can be ascribed to their ability to induce genetic (DNA damage and mutations) and/or epigenetic (DNA methylation) alterations. Both genetic and epigenetic alterations can adversely affect the expression of disease-specific genes.

The current methylome study builds up on our previous work examining DNA damage formation in the oral epithelium of exclusive vapers and smokers. Investigating the genotoxic and epigenetic effects of e-cigarette use can shed light on the molecular pathways affected by vaping vs. smoking and help identify key target genes that can serve as biomarkers for assessing disease risk in vapers vs. smokers.

Additionally, there is a general misconception that e-cigarettes are less harmful than traditional cigarettes because they do not burn tobacco to produce aerosol for inhalation. In this study, we demonstrated that vaping is not risk-free and can produce epigenetic changes in disease-specific genes similar to those caused by smoking. We hope that our findings will raise awareness among adults and teens of the potential harmful effects of vaping.

Healio: How do these new findings impact clinicians? Do you recommend any strategies to help clinicians counsel patients about these risks?

Tommasi and Besaratinia: The scientific data presented in this report can inform evidence-based strategies for tobacco use prevention, which can be adopted by clinicians and other health care professionals. These data can also provide actionable information for regulatory agencies, such as the U.S. FDA, which has the authority to regulate the manufacturing, marketing and distribution of tobacco products to protect public health.

Healio: The FDA announced in June that it has authorized the marketing of four menthol-flavored e-cigarette products. Based on what you have discovered in this study and past research, why is this a step in the wrong direction?

Tommasi and Besaratinia: The accessibility of menthol-flavored e-cigarette products to novice tobacco users, specifically teens and youth, is of special concern. The minty and candy-like flavor, aroma and topical cooling and anesthetic properties of menthol make mentholated tobacco products preferable to new users who struggle to overcome their aversion to certain sensations of smoking or vaping, such as harshness, throat and chest irritation, and stale aftertaste. By easing the discomfort associated with the use of nonmentholated tobacco-products and by smoothening the use experience, menthol-flavored e-cigarettes may serve as a starter product for adolescents, youth and young adults. Therefore, menthol-flavored e-cigarettes can help facilitate transition of novice users from experimentation to regular use and long-term nicotine addiction.

Healio: What do you have planned for future research?

Tommasi and Besaratinia: We are now examining an independent, larger group of participants to learn more about the effects of vaping on DNA methylation. Our goal is to further scrutinize the impact that certain product characteristics, including type of e-cigarette device, e-liquid flavorings and other contents, as well as duration and intensity of vaping, can have on the methylome. We also aim to investigate the persistence or reversibility of the methylation alterations observed in this report, in vapers and smokers, after cessation of tobacco product use.

While the present study highlights the parallels in the epigenetic effects of vaping and smoking, it also identified 409 and 2,021 DMR-associated genes specific to vapers and smokers, respectively. We plan to examine these unique subsets of DMR-associated genes in relation to the chemical composition of e-cigarette vapor and cigarette smoke.

Additional studies are urgently needed to investigate the long-term health effects of vaping and provide the scientific evidence to inform the FDA’s regulation of tobacco products to protect public health.

References:

• Birdsey J, et al. MMWR Morb Mortal Wkly Rep. 2023;doi:10.15585/mmwr.mm7244a1.
• Tommasi S, et al. Am J Respir Cell Mol Biol. 2024;doi:10.1165/rcmb.2024-0207OC.
• First genome-wide comparison of vapers and smokers finds similar DNA changes linked to disease risk. https://keck.usc.edu/news/first-genome-wide-comparison-of-vapers-and-smokers-finds-similar-dna-changes-linked-to-disease-risk/. Published Aug. 12, 2024. Accessed Aug. 12, 2024.