And How You Could Help Science!Critics of vaping often point out that “we don’t have enough long-term studies” to really know how much risk vaping poses to users. While the Royal College of Physicians and Public Health England have famously estimated that vaping isn’t likely to pose more than 5% of the risk of smoking, there is still some truth to this claim. Vaping just hasn’t been around for long enough to track users for decades to work out what the precise risks are.
So how do the RCP and PHE feel confident enough to make estimates of how much safer vaping is in comparison to smoking?
They use short-term evidence. While there will always be uncertainty surrounding how much you can conclude from short-term changes, any direct comparisons between smoking and vaping have consistently shown that vaping does much less damage.
But unfortunately, that same short-term evidence is often presented in a less-than-helpful fashion. The recent study on DNA damage and vaping was widely-reported as proof “vaping causes cancer,” when in fact it was nothing of the sort, and crucially didn’t compare vaping to smoking.
How vaping affects the DNA is an important topic. It has the potential to inform estimates of the risk posed by vaping in comparison to smoking, especially as we improve our understanding of the consequences of changes to the DNA. This is why getting reliable evidence on the effect of vaping on the DNA (with the crucial comparison to smoking) is absolutely vital.
The good news is that a piece of research exactly like this is in the pipelines. A new study will be focusing on DNA methylation in vapers in comparison to smokers, with the aim of revealing potential differences in long-term risk.
The study looks promising, but the researchers are struggling to recruit enough participants to get it off the ground. If you’re eligible, this is a great opportunity to help increase our knowledge of vaping and its potential benefits in comparison to smoking.We’ve spoken to researcher Dr. Suzi Gage from the University of Liverpool (who you may also know from the Say Why to Drugs podcast) about DNA methylation, her upcoming study and how vapers can help.
DNA Methylation: What it is and Why it MattersDNA methylation is a complicated topic to delve into, but it’s essentially plays a role in gene expression – i.e. how the information from the genes is used by the body to make proteins. Dr. Gage explained:
Everyone has a unique genetic code (or genome) which is made of DNA, is in every cell in your body and provides a “blueprint” of who you are. But other factors influence how your genome is read i.e. how easy it is for proteins to be coded from various parts of DNA. One such factor is DNA methylation: a form of epigenetics (literally meaning “above” genetics).The technical details of what methylation is involve the addition of a “methyl” (CH3) group to the DNA strand, usually in a specific spot on one of the four main components of DNA, cytosine. Methylation happens throughout the genome, but the specific distribution of locations is expected to be linked to the risk of certain conditions. For example, the methylation of certain gene sequences could lead to “tumour suppression” genes being silenced.We asked Dr. Gage about what we know about the relationship between DNA methylation and cancer:
In terms of how it relates to cancer risk, this is something that's being investigated at the moment. DNA methylation changes are widespread in the genetic code of tumours and there's some suggestion that changes in DNA methylation might predict later risk of cancer. We don't fully understand why this might be, yet.
Smoking and DNA MethylationIt shouldn’t come as much of a surprise that smoking impacts your DNA and is thought to have an impact on the process of DNA methylation. Dr. Gage comments:
Similar to how we can look across the whole genome to see whether certain genetic variants predict various things, like disease or behaviours, we can also look at locations across our genome where DNA methylation is different between individuals. When this has been done in the past, it shows that people who smoke have consistent differences in DNA methylation profiles than people who don't smoke. We think that these differences are caused by smoking, but this is a hard thing to confirm - causation is notoriously difficult to prove.In line with Dr. Gage’s comments, a 2016 study of almost 16,000 participants found that smoking-related methylation sites were linked to over 7,000 genes, which is around a third of human genes overall. The most robust results they found were linked to genes associated with smoking-related diseases such as cardiovascular disease and some cancers. Although most of the methylation sites returned to levels typical for non-smokers five years after quitting, some changes persisted for a massive 30 years after quitting.
Researchers have several theories as to how smoking might alter methylation. One possibility is direct damage to the DNA as a result of the cancer-causing chemicals in smoke, with the repair process leading to methylation of the nearby sections of the DNA, and another possibility is that nicotine itself affects gene expression, which may have impacts on methylation. Other possible reasons are related to carbon monoxide reducing the amount of oxygen in tissues, or smoke could act indirectly through DNA binding factors.As Suzi commented, the role of smoking in the differences in smokers’ methylation profiles is hard to prove, but it’s strongly suspected to be a key factor. If the suspected link between methylation and the risk of cancer and other diseases is valid, this all means that looking at methylation could be a good way to estimate future risk.
Vaping and DNA: What Do We Know So Far?At the moment, there isn’t much evidence about vaping and the DNA. So far – as is quite common for vaping – there are only a few small studies and the results are generally contradictory.
One study from late 2016 (from British American Tobacco) used the Ames test (which tests for DNA mutations using bacteria) to compare smoke to vapour from e-cigarettes. The results showed that vapour had no effect after three hours of continuous exposure, whereas cigarette smoke did after just 24 minutes.
Another study from 2017 was widely-reported as finding that vaping causes as much DNA damage as the smoke from an unfiltered cigarette. The researchers used a unique 3D-printed setup for the study, and while the reliability of this is questionable, the lack of clarity about the methods used means that dry puffs could have been a factor. However, the results still stand and despite some uncertainty, offer another piece to the puzzle.
The most recent study on the topic looked at the effect of vapour on mice and the effect of nicotine and a nitrosamine on cultured human cells (i.e. cells in a dish). The results were widely-reported as “vaping causes cancer,” but this overstated what the study was capable of finding, to say the least. The study found DNA damage in the lungs, bladder and heart of mice exposed to vapour, as well as issues in the human lung and bladder cells too. However, there was no comparison to smoke in the study, and it’s very difficult to extrapolate from effects seen in mice or cells in a dish to real-life humans.
The biggest issue, though, is that the authors attribute their results to nitrosamines, but we have existing evidence about nitrosamine levels in real-world vapers. Peter Hajek commented to the Science Media Centre that:
No comparison with conventional cigarettes was made, but in the text of the article, the authors acknowledge the key bit of information that is of crucial relevance in this story: Vapers show a reduction in these chemicals of 97% compared to smokers. They should have added that his may well be the level that non-smokers obtain from their environment.Simply put, even if the authors were right about the theory, other evidence shows that vapers have much less of these exact same chemicals than smokers. The headlines are reaching way beyond what animals and disembodied cells can really tell us about potential effects in humans, but this fact really drives home the need for a comparison with smoking, and the likelihood that vaping is much, much less damaging.With all this considered, it’s clear there are a lot of gaps to fill in when it comes to vaping and the DNA, and Dr. Gage’s new study aims to do just that.
The Upcoming Study on Vaping and DNA MethylationAgainst this backdrop – as well as the general public uncertainty surrounding vaping – the benefits of the upcoming study become abundantly clear. The more information we can get about vaping and the DNA the better, especially if it makes the crucial comparison with smoking.
We asked Dr. Gage about the main aim of her research:
We are trying to compare the DNA methylation profile of vapers, with that of smokers and non-smokers. We predict that there will be some similarities between smokers and vapers - because most vapers will be consuming nicotine, like smokers will. However, given that the really harmful substances in cigarettes and cigarette smoke are seen at vastly lower magnitude, if at all, in e-cigarettes and vape, we also expect there to be plenty of differences between the methylation profiles of vapers and smokers.If the differences in methylation profiles the researchers expect are supported by the data, there’s a chance it could lead to a better understanding of the relative risk of vaping compared to smoking. Dr. Gage points out the need for caution in interpreting the results, but is generally optimistic about what it could tell us:
It's too early to be sure what these differences in DNA methylation might mean - they could be directly involved in the impact smoking has on cancer risk, but we don't know that for certain yet. Alternatively they might be what are known as 'biomarkers' for cancer - so indicators of an increased risk, but not necessarily the reason for the increased risk themselves.Either way, if we see this difference between vapers and smokers that we predict, this could give us a glimpse about potential differences in long-term risk between smoking and vaping, without having to wait many years. And as the basic science around DNA methylation is also improving, it might well one day give us an idea about the magnitude of cancer risk from vaping, and how that compares to the huge risk of cancer from smoking.
Could You Participate in the Study? Here’s How to HelpThe biggest barrier to completing the study at the moment is the issue with finding enough participants, as Dr. Gage explains:
We're finding it really difficult to recruit vapers - because we need to find vapers that have very rarely smoked.The challenges Dr. Gage and the research team are facing ultimately come down to the fact that most vapers have already smoked, contrary to some of the claims that e-cigarettes are “recruiting a new generation of nicotine addicts.” But without vapers that haven’t smoked, the results will be really hard to interpret.
As I've mentioned, smokers have a very distinctive DNA methylation pattern, and the problem we have is that this pattern remains even after a person has quit smoking, potentially for many years. If we recruit vapers who have used vaping to quit smoking, we might just see the 'smoking' methylation pattern in vapers, because it's still there after they've quit.
This is why we're trying to recruit people who've smoked very few cigarettes (less than 100) in their lifetime, to hopefully minimise this problem. The problem is, as you might predict, the vast majority of people who use e-cigs do so to quit smoking, so we're struggling a bit.
If you meet the criteria for the study and want to participate, you’d not only be helping the researchers, you’d likely be part of a piece of research that emphasises the benefits of vaping over smoking overall. So for anybody reading who vapes but has smoked less than 100 cigarettes in your life, we asked Dr. Gage what participants need to do:
The study is really simple - we ask people to fill out a 5-10 minute online questionnaire about their smoking and vaping habits. Then we will post them out a kit to collect their saliva so we can link their vaping or smoking behaviour with their DNA methylation profile. We'll even send a pre-paid envelope for them to return the kit to us without any cost to themselves.Here's the link with all the information and the online questionnaire.
If you need any more encouragement, you’ll also be entered into a prize draw with the chance to win £100, £50 or £20 if you take a few minutes to fill out the questionnaire and give a sample of your saliva. So there’s a chance you’ll get £100 for five minutes of your time and a bit of spit!
Dr. Gage says they’re hoping to have the results collected in the next few months, so if you’re eligible, don’t hesitate to get involved! It’s a fantastic opportunity to contribute to our understanding of vaping and support high-quality research that looks at vaping with the crucial comparison to smoking in mind. If the researchers find what they’re expecting, it will be a clear demonstration of the benefits of switching to vaping for smokers.
We’d like to say a big thank you to Suzi for answering our questions and telling us more about her upcoming research!