E-cigarettes damage human cancer-related DNA as much as cigarettes

The scientific evidence that e-cigarettes cause cardiovascular and pulmonary disease is more extensive than for cancer, probably because these diseases are manifest faster than cancer, which can take years.  One way to gain insight into the relationship between e-cigarette use and cancer risk is to look for DNA damage that, over the long term, may initiate biological changes that can lead to cancer.

Stella Tommasi, Hannah Blumenfeld and Ahmad Besaratinia did just that in their important new study, “Vaping Dose, Device Type, and E-Liquid Flavor are Determinants of DNA Damage in Electronic Cigarette Users,” published in Nicotine and Tobacco Research. They analyzed cells taken from the inside cheeks (oral epithelial cells) of vapers, smokers, and people who had never vaped or smoked. They found that vapers and smokers had similar levels of DNA damage—more than twice the amount found in non-users.

Both genes are significantly more damaged among e-cigarette users and smokers than among non-users. There are not significant differences between e-cigarettes and cigarettes. (Adapted from Figure 1 of their paper)

DNA damage to two genes (POLB and HPRT) in these cells was measured as an indicator of assault to the genome. DNA damage is an early change, which may trigger events that can lead to disease development. In fact, DNA damage is associated with an increased risk for many chronic diseases, including cancer and inflammatory diseases. 

Many people who use e-cigarettes are current or former smokers, which complicates assessing the effects of e-cigarettes.  Indeed, e-cigarette advocates often use this fact to dismiss evidence linking e-cigarettes to disease, even in studies that control for cigarette use.  Tommasi and colleagues avoided this problem by only studying people who had never smoked and just used e-cigarettes or never used e-cigarettes and just smoked.  Non-users had never used either product.

More use more damage

DNA damage was higher among those who vaped or smoked more frequently. It was also higher in vapers who used vape pods and mods, as well as sweet-, fruit- or mint-flavored vapes.

In terms of devices, vapers who used pods had the highest levels of DNA damage, followed by those who used mods. In terms of flavors, sweet-flavored vapes were linked to the highest levels of DNA damage, followed by mint/menthol- and fruit-flavored vapes.

The new study builds on earlier research from Besaratinia and his team, which showed that vaping is linked to alterations in gene expression, epigenetic changes, and other biological changes that are implicated in disease development.

Another important finding is that the effects of vaping and smoking were similar despite the fact that e-cigarettes deliver lower levels of some carcinogens and other toxicants than cigarettes.  The similar effects of e-cigarettes and cigarettes may be due to the presence of compounds in e-cigarettes that are at lower levels or not present in cigarettes, nonlinear dose-response effects, or both.  This study adds to the evidence base that measuring levels of exposure to a limited number of toxicants in e-cigarette (or other tobacco product) aerosol is not a good measure of actual harm.

Here is the abstract:

Introduction: Despite the widespread use of electronic cigarettes, the long-term health consequences of vaping are largely unknown.

Aims and methods: We investigated the DNA-damaging effects of vaping as compared to smoking in healthy adults, including “exclusive” vapers (never smokers), cigarette smokers only, and nonusers, matched for age, gender, and race (N = 72). Following biochemical verification of vaping or smoking status, we quantified DNA damage in oral epithelial cells of our study subjects, using a long-amplicon quantitative polymerase chain reaction assay.

Results: We detected significantly increased levels of DNA damage in both vapers and smokers as compared to nonusers (p = .005 and p = .020, respectively). While the mean levels of DNA damage did not differ significantly between vapers and smokers (p = .522), damage levels increased dose-dependently, from light users to heavy users, in both vapers and smokers as compared to nonusers. Among vapers, pod users followed by mod users, and those who used sweet-, mint or menthol-, and fruit-flavored e-liquids, respectively, showed the highest levels of DNA damage. The nicotine content of e-liquid was not a predictor of DNA damage in vapers.

Conclusions: This is the first demonstration of a dose-dependent formation of DNA damage in vapers who had never smoked cigarettes. Our data support a role for product characteristics, specifically device type and e-liquid flavor, in the induction of DNA damage in vapers. Given the popularity of pod and mod devices and the preferability of sweet-, mint or menthol-, and fruit-flavored e-liquids by both adult- and youth vapers, our findings can have significant implications for public health and tobacco products regulation.

Implications: We demonstrate a dose-dependent formation of DNA damage in oral cells from vapers who had never smoked tobacco cigarettes as well as exclusive cigarette smokers. Device type and e-liquid flavor determine the extent of DNA damage detected in vapers. Users of pod devices followed by mod users, and those who use sweet-, mint or menthol-, and fruit-flavored e-liquids, respectively, show the highest levels of DNA damage when compared to nonusers. Given the popularity of pod and mod devices and the preferability of these same flavors of e-liquid by both adult- and youth vapers, our findings can have significant implications for public health and tobacco products regulation.

The full citation is: Tommasi S, Blumenfeld H, Besaratinia A. Vaping Dose, Device Type, and E-Liquid Flavor are Determinants of DNA Damage in Electronic Cigarette Users. Nicotine Tob Res. 2023 Feb 14:ntad003. doi: 10.1093/ntr/ntad003. Epub ahead of print. PMID: 36780924.  It is available here.

The USC press release for this study is here.

Published by Stanton Glantz

Stanton Glantz is a retired Professor of Medicine who served on the University of California San Francisco faculty for 45 years. He conducts research on tobacco and cannabis control and cardiovascular disease/

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