Do Studies Show Vaping Causes Cancer? No.

In February 2022, the World Journal of Oncology published an article by a team of 13 researchers claiming that vapers are about as likely to get cancer as people who smoke traditional cigarettes. 

Citing this article, Stanton Glantz, a tobacco-control activist and retired professor of medicine at the University of California, San Francisco, claimed that not only are there "some carcinogens in e-cigarette aerosol," but "now there is also direct evidence that people who use e-cigarettes are at increased risk of some cancers."

And then the World Journal of Oncology's editors retracted the study because "concerns have been raised regarding the article's methodology, source data processing including statistical analysis, and reliability of conclusions."

The study is indeed riddled with errors. One section, for example, says 2.3 percent of cancer patients in the study vaped and 16.8 percent smoked traditional cigarettes, while the table cited in that passage showed 1 percent of cancer patients in the study vaped and 46.1 percent smoked traditional cigarettes.

As Reason's Jacob Sullum has noted, the retracted study also suffered from another basic flaw, shared by other studies that weren't retracted but probably should have been: It doesn't take into account when its subjects started vaping versus when they were diagnosed. An analysis in Internal and Emergency Medicine cited 11 studies with this problem. As Sullum notes, this is also the reason that a 2020 study claiming to show that vaping causes heart attacks was retracted.

These studies use large observational databases to see if vapers are more likely to have health problems than nonvapers. Although the National Center for Health Statistics claims that the data are representative of the overall population, they're actually not well-suited to studies of this sort. The data are based on self-reports that are often wrong and may contain missing or inconsistent entries. Important information wasn't collected. The databases are not random population samples because only about half the invited subjects agreed to participate and it's likely that certain groups are over- or underrepresented because ​​they face different incentives when deciding whether or not to sign on.

The retracted study claimed a large sample size with data on 154,856 subjects. For assessing the cancer risk of vaping versus traditional smoking, what we should be looking at are vapers who never smoked traditional cigarettes, yet have cancer. There were 180 vapers with cancer in the study. But based on general population percentages, probably fewer than 100 had never smoked traditional cigarettes. That's too small a sample to draw robust conclusions. The median age of vapers in the study was 25, versus 62 for traditional smokers, and they had very different breakdowns of income, race, sex, and medical conditions. Adjusting for all these factors would require a minimum of 1,000 observations.

The editors of the journal and the paper's peer reviewers failed to notice the study's many flaws prior to publication, but they ultimately concluded that it was bad enough to retract. Even so, it's worth dwelling on its problems because they're typical of what we see with statistical studies on this topic and others like it.

If researchers can query the same datasets and arrive at completely bizarre results that are as strong as or even stronger than the ones they're reporting, they're doing something wrong. In this case, the authors claimed active vapers had 2.2 times the risk of cancer as the control group. But their logistic regression showed that people who never used cocaine, heroin, or methamphetamines also had a 2.2-times-higher risk of getting cancer. Why didn't the authors run with this finding—that cocaine might be a cancer preventative? Because it's absurd and would have brought ridicule.

According to the researchers' data, being white raises your cancer risk by 2.6 times. Having a middle income of between $25,000 to $65,000 raises your risk 2.3 times. The authors didn't report these spectacular findings either. This paper is among the worst of the anti-vaping studies that managed to get published in respectable, peer-reviewed journals and cited by regulators and legislators. But even the best studies haven't surmounted a key statistical issue, and they tend to distort the evidence to make vaping look dangerous.

The Internal and Emergency Medicine analysis noted 11 flawed studies that linked vaping to various diseases. Some of those studies relied on surveys that don't report when respondents began vaping. But the Population Assessment of Tobacco and Health Study reports age ranges for initiation of smoking and vaping as well as diagnoses. Based on that survey, the authors of the Internal and Emergency Medicine article found that subjects diagnosed with cancer typically started vaping after they were diagnosed with their conditions. In fact, just 4 percent of e-cigarette users were definitely diagnosed after they started vaping. By contrast, about 98 percent of smokers were diagnosed after they started smoking. Overall, 99 percent of cases involved people with a history of smoking, and just 2.3 percent of vapers diagnosed with one of the four health conditions covered by this study had never been cigarette smokers.

The tiny population of vapers who never smoked traditional cigarettes and who started using e-cigarettes before being diagnosed with a health condition is hard to identify, unrepresentative of the general population, and likely too small to draw conclusions from. No amount of tricky statistical work can overcome this basic data issue.

There's another problem with the way the results of these studies are reported. Even if it does turn out that vaping has negative health consequences, it still may be a net positive for users who otherwise would go back to traditional cigarettes. And banning e-cigarettes altogether would cause some people to turn to the black market to get their vaping fix. Then they would have no idea what they're sucking into their lungs because there would be no quality control. In 2019, underground manufacturers of marijuana vapes mixed vitamin E acetate into their products, which likely explains why 2,807 people ended up hospitalized and 68 died.

Proving that traditional cigarettes cause cancer, which they do, required two types of data: observational studies and experimental studies. First, people noticed that cancer patients were more likely to be smokers than noncancer patients, and then careful experimentation teased out some of the mechanisms by which smoking led to cancer.

Observational studies, even without data issues, can show only an association, not causation. Although most vaping studies claim only an association, journalists, activists, and public officials are quick to assert causation. Experimental studies can show causation but can't measure the practical extent of an issue or possible offsetting factors.

One experimental study of vaping that drew press attention was published in the Journal of Nuclear Medicine under the title "Molecular imaging of pulmonary inflammation in electronic and combustible cigarette users: a pilot study."

One problem with this particular paper is that it studied only 15 people: five vapers, five users of traditional cigarettes, and five people who don't smoke at all. However carefully you select groups of five subjects, they can't represent a broad enough cross-section of users to draw any solid conclusions. That would require hundreds of participants. This experiment also relied on screening volunteers and made no attempt at randomness or sampling the range of the population, meaning that each of the three groups of five subjects differed from each other in important ways.

The paper did not show that vaping causes lung damage—in fact, the researchers didn't check for that. Instead, it looked at "biomarkers," or chemicals thought to be associated with lung damage. By that measure, they found no difference between the five vapers and the control group of five people who had never vaped or smoked.

The study did find that uptake of a chemical thought to react to a biomarker for lung damage was higher in the five vapers than in the control group. But the five cigarette smokers included in the study had a lower uptake of that chemical than the controls, which makes the conclusion suspect since we know traditional cigarettes cause lung damage. Most likely, this correlation can be attributed to random chance. And this was a pilot study, meaning it was aimed not at generating firm conclusions but at testing procedures and determining which hypotheses could be tested in a subsequent study.

The authors mentioned more than 30 statistical tests at the 5 percent level of significance, and they may have conducted more. A 5 percent significance level means there is a 5 percent chance of getting a positive result by random chance even if there is no association at all in your data. With 30 tests, you should expect 1.5 positive results even if vaping is unrelated to lung health. The authors got two positive results out of 30, which is hardly strong evidence of anything. And the two results are among the least direct in terms of linking vaping to lung damage. The more direct tests of biomarkers failed to find any differences among the groups.

A classic prohibitionist argument is that while a controversial activity may not be harmful in itself, it leads to bad things. In the case of vaping, several studies suggest that young vapers are something like seven times as likely to smoke traditional cigarettes in the future than similar young people who don't vape.

An oft-cited paper in this area, "E-Cigarettes and Future Cigarette Use," is typical of the genre. Out of 298 Southern California 17-year-old high school students who didn't vape, only 11 percent were smoking cigarettes a year later. Among those who were vaping at 17, 40 percent had taken up old-fashioned cigarettes at 18.

The paper did a lot of additional analysis, but this is the basic statistic driving the conclusion. To the authors' credit, they were careful to label this as an "association" between vaping and future smoking rather than claiming that vaping caused future smoking. Yet when this paper was cited by regulatory authorities, they interpreted it as causal evidence and therefore as a justification to restrict vaping.

There are reasons to be skeptical about this kind of research. Not everyone is honest when they fill out a survey, especially young people asked about activities that are frowned upon. And only 14 percent of the students interviewed at age 17 participated in the follow-up survey a year later. The missing students might be systematically different from the ones recorded in the study.

It's also plausible that teenagers who vape differ from teenagers who don't in ways that independently affect their likelihood of smoking. Perhaps the type of kid who vapes at 17 is more likely to smoke at 18. In that case, restricting vaping among 17-year-olds probably won't reduce smoking at age 18. In fact, some 17-year-old vapers will switch to traditional cigarettes or turn to underground purveyors of e-cigarettes, which would pose a much more serious health risk. There is plenty of evidence that many smokers use vaping to reduce or quit smoking. In fact, adolescent smoking has continued to fall as adolescent vaping has increased.

Another anti-vaping argument is that it has negative mental or social health consequences. Studies like "Electronic cigarette use and mental health: A Canadian population-based study" suffer from the same issues as studies linking vaping to future smoking. It's easy to show that vapers have more psychological and social issues than nonvapers, but that's only an association. An obvious alternative explanation is that troubled kids are more likely to vape—either as a form of self-medication, or because they have less regard for adult opinion and rules, or perhaps because they are less supervised or have less to lose by acting in a deviant way.

Even if we did have good observational studies suggesting that vaping is reliably associated with future smoking, or that vaping is associated with mental and social problems, we would need experimental studies to support causal claims. Most real experiments are unethical since participants would have to be randomly assigned to vape or avoid vaping, which is why researchers look for natural experiments.

A good example of a natural experiment is "Intended and unintended effects of e-cigarette taxes on youth tobacco use." The authors used data on youth smoking and vaping rates in 10 states and two large counties that enacted e-cigarette taxes between 2010 and mid-2019. They found that taxes were associated with a reduction in vaping among young people. But they were also associated with an increase in young people smoking traditional cigarettes. That's good evidence that vaping and smoking are substitutes. If vaping led to smoking, a decrease in vaping would lead to a decrease in smoking.

Several other natural-experiment studies reinforce the idea that vaping and smoking are substitutes, although the rate of substitution seems to vary in different populations. While we still have a lot to learn in this area, the evidence to date suggests that discouraging vaping will lead to increased smoking and very likely worse public health.

This research suggests that the 15–20 percent e-cigarette tax, which was part of the original Build Back Better Act though was eventually taken out, probably would have reduced youth vaping by about 3 percent and increased youth smoking by about 2 percent. Given the evidence that vaping is far less hazardous than smoking, more teens smoking instead of vaping doesn't represent an improvement in public health. None of this research shows that vaping is safe, and it doesn't rule out the possibility of negative health effects that haven't yet been found. But in public policy, the most important question is: "Instead of what?"

In real life, there are no solutions, only trade-offs. There's overwhelming evidence that if the alternative to vaping is cigarette smoking, vaping represents a huge improvement for public health. Government officials generally fail to reason in these terms. They tax, ban, and regulate as if their policies exist in a vacuum, citing statistically dubious studies to support their preconceived policies.

Photos: Douglas Graham/Newscom; Peggy Peattie/TNS/Newscom; Stanton Glantz by Noah Berger

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