Pre-Clinical Study Suggests E-Cigs May Lead to Lung Cancer in High-Risk Individuals

By Lindsay Fox Posted February 12, 2014

electronic cigarette vapor may lead to lung cancer

 

One of the most well-known and significant risks of smoking is that of lung cancer. The fact that e-cigarettes offer nicotine without the vast quantities of cancer-causing chemicals you’d find in a tobacco cigarette is one of the main reasons smokers choose to make the switch in the first place.

 

However, a new  pre-clinical study presented at a conference last month has called this theory into question, suggesting that human lung cells with mutations associated with a high cancer risk exhibit more “cancerous behaviors” after being exposed to e-cigarette vapor.

 

The details of the research need to be filled in, but the potential of the finding is so surprising that it warrants further investigation.

 

The Study – Exposing Mutated Cells to Smoke and E-Cig Vapor

 

Firstly, it must be stressed that this was a pre-clinical study, effectively a first-line of research which is used to determine whether a relationship exists and therefore if it warrants further investigation.

 

Cigarette SmokeIn this study, the researchers investigated the effect of e-cigarette vapor and cigarette smoke on cultured lung cells bearing mutations in the P53 and KRAS genes. According to lead author Stacy J. Park, Ph.D., “Mutations in the genes P53 and KRAS are often found in the airways of current and former smokers at high risk for lung cancer.” The cells were grown in a liquid medium which had been exposed to either electronic cigarette vapor or tobacco smoke for four hours.

 

According to the published abstract of the study (aside from news reporting, the only information available on the research), the cells were either exposed to e-cig vapor with a low nicotine concentration chosen to replicate the amounts found in the blood of vapers or a higher concentration. This higher concentration was chosen as an estimate of the nicotine levels the cells would be exposed to in real-world usage, although this concentration is not revealed in the abstract. Additionally, some cells were exposed to tobacco smoke and some were left untreated to enable comparison.

 

electronic cigarette vaporWith regards to the results, Park commented, “We found that e-cigarette exposure enhances the aggressive behavior of human lung epithelial cells that have P53 and KRAS mutations. As a result, we think that e-cigarette exposure could contribute to lung cancer in individuals at high risk for the disease. Clearly, our results are very preliminary, and much more research is needed to better establish the role of e-cigarettes in lung cancer. But I think they show that people should approach e-cigarette use with caution and not assume it is safe.”

 

Reporting from sites such as MedicalXpress explains that the cells exhibited cancer-like behaviors in both the e-cigarette vapor and tobacco smoke conditions. These included things like colony formation, which is an integral process for the survival and the spreading of cancer. There were also changes in gene expression similar to those seen in the tobacco smoke medium.

 

So, E-Cigs Promote Lung Cancer, Right?

 

There are some important extra pieces of information added by the abstract which didn’t make it into the press reporting.

 

Firstly, the abstract explains that invasive behaviors occurred in the mutated genes at baseline (with no tobacco smoke or e-cig vapor) due to the specific mutations chosen. KRAS gene mutations are known risk factors for cancer, but not thought to be a direct cause, according to the National Institutes of Health’s Genetics Home Reference site. The P53 protein is a tumor suppressor, which basically means that it inhibits the growth of cancers. In this research, it was “silenced,” so it doesn’t seem too surprising that invasive behaviors occurred even in the absence of smoke or vapor. The abstract also suggests that colony growth occurred in the untreated sample, by saying that the high-nicotine sample “enhanced colony growth […] compared to the untreated and low nicotine treatment groups.”

 

The MIT website has some useful information about the impact of both of these mutations when used in mouse models of cancer, “Combining mutations in K-ras and p53 in the lung led to the development of more advanced tumors, which exhibited desmoplastic stroma, increased invasiveness and metastatic potential.” In other words, the mutations chosen tend to produce aggressive cancers with high potential to spread.

 

Research into snus (which contain the same trace carcinogens as e-cigs in larger quantities) has shown that P53 mutations are not common in users, so it seems reasonable to assume that these wouldn’t be common in vapers either.

 

Additionally, the results in the abstract make it clear that the low and high nicotine conditions did not have the same impact. The lower nicotine concentration (the one based on actual plasma nicotine levels in vapers) wasn’t toxic to the cells, and it didn’t promote additional growth of colonies. The high-nicotine (at an unstated concentration) and tobacco smoke did enhance colony growth, after the cells were exposed to the medium for 10 days. Similarly, with the findings related to changes in gene expression, it was the high nicotine condition which produced cigarette-like changes, and this occurred after 96 hours of exposure.

 

Conclusion – Lots of Questions, Too Few Answers

 

Sadly, e-cig researchers such as Dr. Farsalinos and Dr. Siegel have not yet addressed the research in their always illuminating blog posts which delve deeper into findings like this. As non-geneticists, non-doctors and non-experts, we join Steve K. in anxiously awaiting one of them to provide some informed analysis on this research. Even to a layman, however, it’s clear that there is much more to this story than “e-cigs promote lung cancer in those at-risk.”

 

With an unclear nicotine content in the tests producing headline-friendly, tobacco-like results, the seemingly long periods of exposure and the apparently expected cancer-like behavior from the combination of mutations, there is clearly more information that needs to be provided in order to comprehend the significance of these findings, and we haven’t yet been deemed worthy of finding it out through news reporting.

 

E-cigarettes do need to be researched further, but it doesn’t escape notice that any claim of significant harm from them is riddled with anything from uncertainty – as is abundant in this case – to outright misappropriation of findings. Whether this study will require down-grading to the ranks of “misleading nonsense” is yet to be seen.

 

Articles related to “e-cig vapor”

 

  • Study: Is Second-Hand E-Cigarette Vapor Dangerous? A new piece of research has investigated the concentrations of nicotine, carbon monoxide and various volatile organic compounds after e-cigarette use, and compared them to those from a traditional cigarette.
  • Study: Most E-Cig Vapor Poses No Risk to Heart Cells A new piece of research from Dr. Farsalinos and his colleagues has investigated the potential cytotoxicity of e-cig vapor, and found that the vast majority of vaporized liquids are much safer than the smoke from traditional cigarettes.
  • Review of Existing Evidence Confirms No Risk From E-Cig Vapor A new study, funded by CASAA, has looked at the existing data on the contents of e-liquids and the vapor from e-cigs, and found no evidence of risk to vapers, even under “worst case” scenarios.
  • Typical Vapor Content of an E-Cigarette For the most part, we know exactly what goes into the production of the liquid used in the majority of electronic cigarettes. E-liquid typically consists of four main ingredients: propylene glycol, vegetable glycerin, nicotine and flavoring. What isn’t exactly clear is what constituents make up the vapor e-cigarettes produce.

 

Photo Credit: Liberty Voice (guardianlv.com)

  • http://tobakkonacht.com/ Michael J. McFadden

    This would seem to be the most important note in the Abstract: “The lower nicotine concentration was selected to mimic the average plasma nicotine levels in ENDS users and did not demonstrate toxic or anti-proliferative effects on the cells. The higher concentration was chosen to represent the anticipated nicotine levels to which the epithelial cells of smokers are actually exposed.”

    The problems seem to have been shown ONLY in the second set: i.e. NOT in the set actually approximating that of e-cig users. It would seem that a *clearer* headline for this research would be that they discovered NO such effects to be expected in ordinary “vapers” … but instead it seems to have gotten distorted into implying the opposite.

    Why?

    - MJM

  • http://ecigarettereviewed.com/ Lindsay Fox

    You’re complete right on this! Only the abstract is available (as far as I could tell, at least), and there is no mention of either nicotine level used, which you would think be *the* most important piece of information about the methodology of the research. The second one seems suspect (“represent” and “anticipated” appearing in the description doesn’t inspire much confidence), whereas the first is the average plasma nicotine of vapers, which should be based on past measurements instead of just being plucked out of thin air.

    Why indeed. I read recently on Michael Siegel’s blog about a group of researchers looking to do some work on “third hand” smoking who stated what the findings of their research *would* be in their grant proposal! Basically – “we’ll prove that third-hand smoke is also dangerous, give us some money to do it.” Taking a similarly cynical approach with regards to this research, I’d guess that they set out to show the dangers of e-cigs, purposefully constructed an extreme model to specifically produce cancerous behavior and then exposed it to a vapor with ridiculously high nicotine content for as long as it took to get the answer they wanted. If they did just want to get the “e-cigs promote lung cancer” message out, they’d have known full-well that journalists would regurgitate the press release word for word with some added scaremongering thrown in there for good measure. It was probably always intended to be distorted.

  • http://tobakkonacht.com/ Michael J. McFadden

    Re Siegel: Yep! I think he may have gotten that from TobakkoNacht: I called it “L’ouve Ouroboros” : the egg brought forth from the eternal tail eating snake:

    In June of 2010, a new golden ring was hung out for the grabbing by antismoking grant grabbers. The Tobacco-Related Disease Research Program of the University of California announced it wanted to give away $3.75 million to enterprising researchers willing to cook up studies
    examining the deadly twin threats of thirdhand smoke and cigarette butt
    environmental pollution![i], [ii]

    Almost four million dollars to examine two of the silliest con­cepts in the entire arsenal of antismoking research – thirdhand smoke – which is about a thousand times more innocent than the effectively nonexistent threat of secondhand smoke – and littered cigarette butts which wouldn’t kill off the majority of exquisitely ultrasensitive water fleas even if every smoker in the world dumped their butts in the water for twenty-five
    million years![iii], [iv][1]

    They were basically telling research­ers: “Come up with some good study designs to scare the bejeezus out of people regardless of the facts, and you can walk right home with almost four million Washingtons snuggling nice ‘n comfy ‘n warm in your pocket!” (Who says thar ain’t no Santa Claus?)
    =

    [1] The origin of the standard sound bite about butt pollution involves putting a tenth of a butt in a liter of water and observing the death rate of water fleas. The sound bite breaks down when you determine how many butts it would take to pollute the world’s 1.4 sextillion liters of water. At current smoking rates it actually would take 25,000,000 years. If the research examined health effects upon edible fish instead of water fleas, the time frame of concern moves up into the billions of years!

    [i] http://www.icyte.com/saved/www.trdrp.org/494553

    [ii] Evangelista A. “Thirdhand Smoke Health Threat Suspected,” Your University of California, October 2010 http://www.universityofcalifornia.edu/youruniversity/archive/2010/october/thirdhand-smoke-health-threat-suspected.html

    [iii] Register K. “Cigarette Butts As Litter—Toxic As Well As Ugly,” Underwater Naturalist—Bulletin of the American Littoral Society, Volume 25, Number 2, August 2000

    [iv] Slaughter E, et al. “Toxicity of cigarette butts, and their chemical components, to marine and freshwater fish,” Tobacco Control, 2011, Volume 20, Issue Supplement 1, pp. i25-i29. dx.doi.org/10.1136/tc.2010.040170.

    ===

  • Golf Kahn

    Lindsay, Michael is correct (as is his habit!). This begs for another article on this “study”, clarifying the actual results concerning E-Ciggers vs. the Headline Grab.

  • http://ecigarettereviewed.com/ Lindsay Fox

    I suppose there’s a chance the full study will be peer-reviewed and published at some time in the future, at which point we’ll probably be able to find out what’s actually going on here. I’m guessing it’s nothing to worry about at all.

  • Josh Lewis

    There are some points that are overlooked in the test. Like, they did not talk about – the cause of the cell’s mutation, the standard use of nic level and the time period of the test. I would say more research needs to be done on the topic until then I am happy with my ecig.