Epigenetic changes in smokers v. vapers – Expert Reaction

E-cigarette users experience similar DNA changes to the cells lining their cheeks as smokers, according to new international research. 

These ‘epigenetic’ changes are associated with future lung cancer development in smokers. However, the authors note that it’s not yet possible to determine whether they’re also associated with lung cancer development in people who vape.

The SMC asked third-party experts to comment. Feel free to use these comments in your reporting or follow up with the contact details provided.

Associate Professor George Laking, Director of the Centre for Cancer Research, University of Auckland, comments:

Associate Professor Kelly Burrowes, Auckland Bioengineering Institute, University of Auckland, comments:

“It took at least 50 years before the connection between conventional tobacco smoking and the multitude of smoking-related diseases became clear; vaping has only been widely available for 20 years therefore the long-term health effects are unknown. However, there is mounting evidence – from in vitro and in vivo animal studies and short-term studies in humans – that regular vaping disrupts the normal healthy functioning of the body.

“E-cigarettess use heat to aerosolise a liquid that the user inhales. This aerosol or vape has been found to contain toxicants, with our research finding many flavouring chemicals and heavy metals. While we know that vaping introduces less chemicals and less harmful chemicals than smoking, we don’t really know how this translates to health impacts yet.

“Our research is testing several hypotheses to determine whether vaping leads to the same/similar health impacts of smoking, including studying inflammation (the body’s normal defence mechanism), lung lymphatics, and cardiovascular impacts. This new study and our current research is aiming to predict the long-term health effects of vaping before they become widespread in the rapidly growing vaping population.”

Conflict of interest: None 

Professor Ross Lawrenson,  Professor in Population Health, Te Huataki Waiora School of Health Dean’s Office, University of Waikato, comments:

“Does vaping cause harm? In particular, does it cause lung cancer? To show causation, we need to know the incidence of cancer in vapers compared with non vapers, the strength of the association, whether the association is consistent across different populations, and whether it’s greater in those who vape a lot compared with those who vape less or who have been vaping for a shorter time. Lastly, we need to know whether there is a plausible explanation for why vaping could cause cancer.

“This new study suggests that vaping is associated with epigenetic changes in the lining of the cheek. This could be a plausible explanation for a causal association with cancer, but so far we do not have any evidence that vaping does cause cancer. It’s important to note that smoking has been associated not only with lung cancer but also cancer of the larynx, oral cavity, lip, bladder and cervix.

“These findings are from a group mainly concerned with Women’s Health, and provide support for those who believe vaping will prove harmful. However the paper does not provide sufficient evidence of harmful outcomes that will be needed before the public will be convinced to stop.”

Conflict of interests: none

Dr Mangesh Thorat, Honorary Reader at Queen Mary University of London, said:

“Epigenetic alterations, for example DNA methylation, have been associated with risk of various cancers even though a causal association has not been robustly established. This study utilised a very distinct set of samples from a range of different studies. While such range of samples offers opportunity to address multiple questions, such comparisons could be substantially confounded due to disparate nature of the samples. Indeed, as authors acknowledge, a possibility of gender bias also exists.

“This study observed DNA methylation changes in e-cigarette users that are similar to those in cigarette smokers. However, there is no clear dose-response relationship that one would expect and many of the similar changes occur early on. Therefore, it could be hypothesised that the changes observed here are a stress, wounding and healing response to the e-cigarette vapour and cigarette smoke alike.

“The changes observed may not be the long-term alterations that increase the risk of cancers in smokers. The study findings are interesting as such because these point to a potential for e-cigarette vapour to cause local tissue injury and cellular changes at least in the short-term. The data are not sufficient to comment on long-term harms associated with e-cigarette use, or any association such changes may have with the risk of developing cancer.”

Conflicts of interest: none

Professor Andrew Beggs, Professor of Cancer Genetics & Surgery at the University of Birmingham and University Hospitals Birmingham, said:

“This interesting study shows e-cigarette use is associated with similar damaging changes in methylation in human cells as smoking. Although it doesn’t show a direct causal effect, this study shows that further research must be done to understand the effects of e-cigarettes on human health and whether they could be linked to an increased risk of cancer.”

Conflict of interest statement: No conflicts of interest relevant to this research

Professor Lion Shahab, Co-Director of the Tobacco and Alcohol Research Group, University College London, said:

“This international study used a relatively large number of samples (N>3,500), collected from different sites (saliva, blood, cervix) and comprising different cell types (epithelial, immune and lymphoid), to assess epigenetic changes that may be associated with cancer development. The study included current, ex- and never smokers, and also included a subsample of vapers (N=116) who had never regularly smoked cigarettes.

“This comprehensive analysis confirms well-known epigenetic changes associated with smoking observed in blood, extending this to saliva and specific cell types, as well as identifying novel associations with cigarette smoking, which are also seen in separate cancer tissue and early lesion samples. Crucially, some of the epigenetic changes were also observed in saliva samples from vapers, albeit to a lesser extent and not across all cell types.

“While this study provides useful information about potential corollaries of e-cigarette use also seen with cigarettes, which need to be studied further, in my mind this does not provide proof that e-cigarettes cause cancer for several reasons:

1. It is difficult to assess the extent to which the changes seen here translate into actual cancer development. Most cancers involve complex multicellular and multistep processes involving different biological systems, which can include epigenetic changes. However, these alone are unlikely to tell the whole story.
2. The changes reported here are based on differences seen in smokers, some of which are also replicated in a smaller group of vapers. However, such similarities could be the result of confounding (e.g., if vapers are more likely to engage in a variety of unmeasured harmful behaviours that may drive epigenetic change seen in smokers). This study did not assess or control for this kind of confounding, which is compounded by the fact that the participants from the different datasets used here provided samples from different sites and likely varied in important characteristics.
3. Because the group of vapers studied was relatively small, it was not possible to link epigenetic changes to vaping exposure in a clear dose-response manner. While the authors looked at vaping duration, there is only limited evidence that longer duration was associated with greater changes.
4. The paper does not assess epigenetic changes unique to e-cigarettes but looked at those seen in smokers. This is of importance as we already know that e-cigarettes, compared with cigarettes, expose users to much lower levels of known tobacco-related carcinogens that drive cancer (in part because e-cigarettes do not involve combustion, which generates high levels of harmful chemicals seen in tobacco smoke). This means that the health consequences (and underlying causative processes) of e-cigarette use may be quite distinct from those of cigarettes use. These e-cigarette-specific changes need to be investigated in their own right.

“Notwithstanding these limitations, the findings in this paper highlight the continued need to elucidate the potential impact of vaping on disease, including assessing effects distinct from tobacco exposure. It is important to remember that e-cigarettes are a harm reduction product, not a risk-free product, aimed at those using uniquely harmful cigarettes. This paper does not change this risk calculus and serves to underscore the CMO’s advice: ‘if you smoke, vaping is much safer; if you don’t smoke, don’t vape’.”

Conflict of interest statement: No relevant conflicts of interest 

Professor Peter Shields, Emeritus Professor of Medical Oncology at the Ohio State University, said: