Keck School of Medicine of USC researchers, reporting in the American Journal of Respiratory Cell and Molecular Biology, say that epigenetic changes found in tumor suppressor genes of smokers are also found in people who vape. DNA methylation for smokers, vapers, and non-smokers was measured using samples of oral cells, with the investigators finding significant overlap in methylation patterns among those who smoked tobacco and those who vaped.
In particular, the investigators found a common hypermethylated differentially methylated region (DMR) at the promoter of “Hypermethylated In Cancer 1” (HIC1), a tumor suppressor gene that is often silenced in smoking-related cancers.
“Whereas vapers and smokers differ in number of differentially methylated regions (DMRs), they share striking similarities in the distribution and patterns of DNA methylation, chromatin states, transcription factor binding motifs, and pathways,” the researchers wrote. “There is substantial overlap in DMR-associated genes between vapers and smokers, with the shared subset of genes enriched for transcriptional regulation, signaling, tobacco use disorders, and cancer-related pathways.”
In short, noted lead author Stella Tommasi, PhD, associate professor of research population and public health sciences at the Keck School of Medicine: “Electronic cigarettes are not as safe as some people claim that they are, even if the level of most toxicants and carcinogens present in e-liquid and vapor is generally much lower than that found in cigarette smoke. Our findings indicate that the changes in DNA methylation observed in vapers may contribute to the development of disease, including cancer.”
The Keck study comprised 30 young adults (average age 23.5 years) divided into three groups: vapers (people who vaped at least three times a week for at least six months, but did not smoke), smokers (people who smoked at least three times a week for at least one year, but did not vape) and non-users (people who neither vaped nor smoked). The groups were matched by age, race, and gender, while also accounting for other factors such as alcohol consumption, or eating grilled foods.
The Keck team says their study is the most comprehensive look into the effects of vaping to date, noting that previous studies only queried two to three percent of the of the genetic regions. For their research, the team used a new form of high-resolution sequencing known as whole genome bisulfite sequencing that allowed for the analysis of more than 25 million sites across the genome. Using these data they then looked for DMRs, areas of the genome that were more or less methylated in one group compared with the others. This analysis uncovered 2, 863 DMRs in smokers and 831 in vapers.
Comparing these two groups yielded 346 DMRs that are shared by smokers and vapers, noting that these methylated regions are on gene sites that are known to influence signaling pathways that can drive development of disease—a strong indication that, like smokers, the DNA methylation found in vapers could contribute to the development of disease.
Discovery that one of the DMRs of vapers was located within HIC1 was an important discovery since it has previously been linked with various cancers including those linked to tobacco use and methylation of this gene had not been previously identified in vapers.
The team also noted HIC1 could soon be used as a predictive biomarker, to help clinicians monitors patients and identify cancer to inform early treatments. Further, more than half the DMRs found in vapers are not shared by their smoking counterparts, which is consistent with earlier findings that e-cigarettes produce a range of potentially harmful chemicals not found in tobacco products.
Building on this research, the Keck team is now studying a larger cohort to learn more about how vaping may be impacting DNA methylation. This includes drilling down to find the effects of flavoring and other additives in vaping products, as well as how the duration and intensity of vaping impact DNA methylation.
The intent of the research is to eventually develop a methylation signature for vaping that can be used to determine risks related to vaping in the general public.
