Cancer-Related Genetic Changes in E-Cig Users Reflect Those of Cigarette Smokers

E-cigarette (e-cig) use has been shown to lead to development of some of the same cancer-related molecular changes in oral tissue observed in cigarette smokers, according to results from a recent study by Ahmad Besaratinia, PhD, associate professor of research preventive medicine at Keck School of Medicine, USC, Los Angeles, and colleagues. 

In a recent interview with Pharmacy Learning Network, Dr Besaratinia discussed the basis for and findings of his team’s research, elaborating on the health risks associated with e-cig use. 

How do e-cigs differ from cigarettes?

E-cigs are battery-powered handheld devices that simulate tobacco smoking. Unlike conventional cigarettes that burn tobacco leaves to produce smoke, e-cigs heat a solution, containing a mixture of propylene glycol, glycerin, flavors, and (optionally) variable concentrations of nicotine into inhalable vapor. E-cig use is commonly referred to as ‘vaping,’ and e-cig users are interchangeably termed ‘vapers.’

Why did you and your co-investigators choose to compare the regulation of genes and associated molecular pathways in the oral cells of e-cig/cigarette smokers versus nonsmokers?

E-cigs are promoted as safe alternatives to tobacco cigarettes or as aides to smoking cessation. E-cig use is a pressing public health concern in many parts of the world. This is due to the uncertainties surrounding the potential health consequences of vaping and its effectiveness as a putative harm-reduction strategy. Currently, there is a paucity of data on e-cig safety, and very limited scientific evidence to support the efficacy of vaping in aiding smoking cessation. 

There is also concern that e-cig use may lead to nicotine addiction and smoking, especially among youth. The existing data show that e-cig vapor is not merely ‘water vapor’ as is often claimed in alluring advertisements and marketing campaigns. Chemical analyses of e-cig vapor and liquid have confirmed the presence of many toxicants and carcinogens like those found in cigarette smoke. Although the concentrations of most carcinogenic compounds in e-cig products are much lower than those in cigarette smoke, there is no ‘safe’ level of exposure to carcinogens. Thus, ‘lower levels of carcinogens in e-cig products do not equate to no cancer risk.’ 

It is, therefore, important to investigate whether e-cig-derived carcinogens pose a cancer risk to vapers and/or to non-vapers involuntarily exposed to e-cig contaminants in the environment. Equally important is to determine the magnitude of cancer risk associated with vaping as compared to smoking. 

Cancer is a disease characterized by deregulation of key genes involved in crucial cellular functions, such as growth. Deregulation of these important genes in human cells or tissues can inform about cancer susceptibility. 

To investigate the cancer-causing potential of e-cig use relative to cigarette smoking, we studied gene regulation in oral cells of 3 groups of healthy adults—(1) exclusive vapers; (2) smokers only; and (3) those who neither vaped nor smoked. We focused on oral epithelial cells, which line the mouth, because >90% of smoking-related cancers originate in epithelial tissue, and oral cancer is highly associated with tobacco use. 

Please briefly describe your study, highlighting any significant findings of note.

We have investigated the regulation of genes and associated molecular pathways, genome-wide, in the oral cells of e-cig users and cigarette smokers as compared to nonsmokers. Both smokers and vapers showed abnormalities in regulation of a large number of genes, the vast majority of which being cancer-related genes (79% in smokers vs 62% in vapers). Approximately 26% of the deregulated genes in vapers were identical to those found in smokers. However, the preponderance of deregulated genes in vapers (74%) were different from those of smokers.

The uniquely deregulated genes in vapers are implicated in lung cancer, esophageal cancer, bladder cancer, ovarian cancer, and leukemia. The commonly deregulated genes in vapers and smokers affect a prominent signaling pathway that governs diverse cellular functions, including growth, programmed cell death, and tumor development.

We conclude that e-cig users have the same characteristic deregulation of genes as smokers. The underlying mechanisms of gene deregulation in vapers partly resemble but mostly differ from those of smokers. The latter could be ascribed to the similarities and differences in chemical composition of e-cig vapor and cigarette smoke, respectively.

In view of the increasing popularity of e-cigs, especially among adolescents, and the paucity of regulations on these products, these findings have significant implications for public health and tobacco regulatory science. 

What are the possible real-world applications of these findings in clinical practice? Could they potentially affect existing guidelines for lung cancer screening?

Our whole transcriptome analysis of oral cells from exclusive e-cig users and smokers shows that vapers, similarly to smokers, have deregulation of key genes, the majority of which converging on cancer-related pathways and functions. The extent of gene deregulation and the affected pathways in e-cig users are partly overlapping with, but mostly distinct from, those of smokers. 

To our knowledge, this is the first report to demonstrate that e-cig users have significant deregulation of critically important genes and associated molecular pathways in the oral epithelium, which is a major target tissue for smoking-associated cancer.

Our findings warrant further investigations into the long-term effects of vaping not only in regular e-cig users but also in non-users who are involuntarily exposed to secondhand e-cig vapor (eg, children and fetuses of vaping pregnant mothers). Evidence from research studies, such as the present one, can lay the foundation for development of scientifically based regulations on e-cig manufacturing, marketing, and distribution.