Analysis: Electronic cigarettes and cancer risk

A study hints that e-cigarettes cause the same epigenetic changes found in cancer patients and traditional cigarette smokers. But the study has many limitations.

Cigarette smoking caused over 7 million deaths in 2019

Tobacco consumption causes a number of harmful effects on the body at the cellular, organic, and systemic levels. For example: DNA damage, inflammation, oxidative stress and epigenetic alterations. In 2019, cigarette smoking caused an estimated 7.69 million deaths worldwide, which is expected to rise in the following years.

With the aim of reducing health damage, alternatives to smoking have emerged such as the use of smokeless tobacco and electronic cigarettes, which vaporise a liquid solution often containing nicotine and other chemical compounds. Despite the current scientific consensus in favouring e-cigarettes over traditional cigarettes (the NHS has described them as '95 per cent less harmful'), recent studies have highlighted potential drawbacks. For example, there are concerns on the induction of endothelial dysfunction and DNA damage; highlighting the need for further research into the molecular changes and long-term health impacts of e-cigarettes.

However, the recent introduction of e-cigarettes and the fact that many e-cigarette users are also former smokers, make this research complex. Studies with several decades of follow-up would be needed to investigate the impact of e-cigarette use on cancer risk, with cancer incidence as the primary outcome.

In e-cigarette users, there are changes in DNA methylation 'similar' to those of traditional cigarette smokers

A recent study published in Cancer Research is, according to the authors, a step towards helping researchers better understand the long-term health effects of e-cigarettes. The research analysed the epigenetic effects of tobacco and e-cigarettes on DNA methylation in over 3,500 samples to examine the impact on cells directly exposed to tobacco (e.g. those in the oral mucosa), and those not directly exposed (e.g. in the blood or cervix).

The researchers found that epithelial cells in the mouth show substantial epigenomic changes in smokers. These changes were even more pronounced in lung tumours or precancerous stages when compared to normal lung tissue, supporting the idea that smoking-associated epigenetic changes facilitate uncontrolled cell growth. The publication also includes new data showing that similar epigenomic changes are also observed in the cells of e-cigarette smokers who had smoked less than 100 tobacco cigarettes in their lifetime.

The study authors are unable to state that e-cigarettes cause cancer, but they stress the importance of having found that e-cigarette users exhibit certain epigenetic changes in buccal cells similar to those of smokers. They also hint that these changes could be associated with the future development of lung cancer. The researchers state that further studies are needed to investigate whether these characteristics can be used to specifically predict cancer in traditional cigarette smokers and e-cigarette smokers.

We know too little about the long-term damage of e-cigarettes

Dr Mangesh Thorat, from Queen Mary University of London, said: "Epigenetic alterations, such as DNA methylation, have been associated with the risk of various cancers, although a causal association has not been firmly established. This study used a very distinct set of samples from a number of different studies. Although this range of samples offers the opportunity to address multiple questions, such comparisons could be substantially confounded due to the heterogeneous nature of the samples".

Dr Thorat explains that the study observed changes in DNA methylation in e-cigarette users that were similar to those of cigarette smokers. However, there is not the clear dose-response relationship one would expect and many of the similar changes occur early. Therefore, it could be assumed that the observed changes are an initial stress response to e-cigarette vapour and cigarette smoking.

Expanding on the limitations, Dr Thorat mentions that "the observed changes may therefore not be the long-term changes that increase the risk of cancer in smokers. The data are insufficient to comment on the long-term harms associated with e-cigarette use, or any association of these changes with the risk of developing cancer."

Electronic cigarette for harm reduction?

Associate Professor George Laking, director of the Centre for Cancer Research, University of Auckland, said: "The research finds that e-cigarette users exhibit increased hypermethylation in the cells lining their cheeks, compared to non-smokers. It is said that at least some of these changes were similar to those observed in smokers. One must be careful with the word similar, because it can have many different meanings. For example, a lethal snake is somewhat similar to a harmless earthworm. Importantly, other changes have occurred in the cells of smokers that have not been found in e-cigarette users or non-smokers."

For Prof. Laking, the development of cancer is a multi-stage process. He pointed out that "in this study, we focus on an early stage potentially present in e-cigarette users. This does not seem to me to be particularly new information when considered in conjunction with reports on inflammatory changes in the tissues of e-cigarette users. There are cellular and tissue mechanisms of cancer repair and control that can counteract the effects of such changes. Overall, this paper should not change the public health messages on Vaping to Quit. Vaping remains an essential tool for harm reduction compared to cigarettes."

Research is needed on the specific potential harms of e-cigarettes

Prof Lion Shahab, co-director of the Tobacco and Alcohol Research Group, University College London, said: "The article does not assess epigenetic changes specific to e-cigarettes, but considers those observed in smokers. This is important because we already know that e-cigarettes, compared to cigarettes, expose users to much lower levels of known tobacco-related carcinogens that cause cancer (in part because e-cigarettes do not involve combustion, which generates high levels of harmful chemicals found in tobacco smoke)."

For Prof Shahab, the former signals that the health consequences and causal mechanisms of e-cigarettes use can be very different from those of using traditional cigarettes. It is precisely these changes specific to e-cigarettes that physicians call for further study.

  1. Herzog C, Jones A, Evans I, Raut JR, Zikan M, Cibula D, Wong A, Brenner H, Richmond RC, Widschwendter M. Cigarette smoking and e-cigarette use induce shared DNA methylation changes linked to carcinogenesis. Cancer Res. 2024 Mar 19. doi: 10.1158/0008-5472.CAN-23-2957. Epub ahead of print. PMID: 38503267.
  2. Science Media Centre. Expert reaction to epigenetic changes in cells of smokers and vapers. March 19, 2024