The first genome-wide comparison of vapers and smokers finds similar DNA changes linked to disease risk

In the most comprehensive study of its kind, researchers from USC’s Keck School of Medicine compared epigenetic changes in the genome in young adults who vaped, smoked or did not use nicotine products, finding a tumor suppressor gene among the most affected genes in vapers and smokers.

Young adults who vape exhibit chemical changes in their DNA that are similar to those in young adults who smoke – changes known to be linked to the development of cancer – according to a study published in the American Journal of Respiratory Cells and Molecular Biology.

A team of researchers from USC’s Keck School of Medicine measured DNA methylation, a chemical modification of DNA that can effectively turn genes “on” or “off” in the oral cells of young adult vapers, smokers and non-users.

DNA methylation is vital for normal cellular processes, but when it goes wrong it can lead to cancer and other diseases. Using an advanced genetic sequencing technique, they analyzed virtually the entire genome in the cells of study participants, compared to previous studies that analyzed only two to three percent of genetic regions in vapers or smokers.

The researchers found a substantial overlap in DNA methylation patterns, a type of epigenetic modification, between people who vaped and those who smoked.

“Our findings indicate that the changes in DNA methylation observed in vapers may contribute to the development of diseases, including cancer,” said Stella Tommasi, Ph.D., associate professor of population research and public health sciences at the Keck School of Medicine . and the lead author of the study.

“Electronic cigarettes are not as safe as some people claim, even though the levels of most toxic and carcinogens in e-liquid and vapor are generally much lower than those in cigarette smoke,” she said.

The study, supported in part by the National Institutes of Health, adds to a growing evidence base on the health risks of vaping. It also provides a basis for future research that attempts to identify a molecular signature to assess the disease risks associated with vaping.

In the meantime, the research team hopes the study can further highlight the potential harms of vaping as new products continue to hit the market.

“These findings have significant implications for public health and tobacco regulation, which aim to keep vaping products away from young people, who are a particularly vulnerable population,” Tommasi said.

Comparison of DNA methylation

The study involved 30 young adults, with an average age of 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 vaped at least three times a week). per week), week for at least a year, but do not vape) and non-users (people who do not vape or smoke).

Researchers matched the groups based on age, race and gender. They also took into account possible confounding factors, including how much alcohol or grilled food each participant consumed.

After collecting oral cell samples from each participant’s cheeks, the researchers used a high-resolution sequencing technique known as whole-genome bisulfite sequencing to study more than 25 million locations in the genome.

They looked for differentially methylated regions (DMRs), or areas of the genome that were more or less methylated in one group of participants than in another. They found 831 DMRs in vapers and 2,863 in smokers.

The researchers then looked for DMRs shared between smokers and vapers, finding 346 (46% of all DMR-associated genes in vapers) that overlapped between the two groups. These methylated regions were located at gene locations known to regulate key biological signaling pathways that drive disease development.

This indicates that DNA methylation in vapers, just like in smokers, may contribute to the development of diseases such as cancer, Tommasi said.

A key finding from the study was that the key DMR most shared between vapers and smokers was in HIC1, a tumor suppressor gene called Hypermethylated In Cancer 1 due to the extensive research base linking it to several cancers, including those related to tobacco. usage.

HIC1 is altered by methylation at a very early stage of cancer development. Methylation of HIC1 has also been found in blood samples from smokers who are at high risk for cancer and other chronic diseases. This means it could be useful as a predictive biomarker to help identify people who need close monitoring so that cancer can be diagnosed early, when it is easiest to treat.

“This is an exciting discovery because the methylation of this gene has never before been identified in vapers,” Tommasi said.

Of note, more than half of DMRs found in vapers are not detected in smokers. This finding is consistent with the fact that e-cigarettes produce a wide range of harmful or potentially harmful chemicals, some of which are not found in tobacco cigarettes, the researchers said.

Zooming in on the impact of vaping

The research team is now studying a separate, larger group of participants to learn more about the impact of vaping on DNA methylation. They want to know whether the types of flavors and additives in e-cigarettes, as well as the duration and intensity of vaping, affect DNA methylation.

Their goal is to establish a molecular signature for vaping that can be used to assess the risks of vaping in the general population.

“This study offers many opportunities,” she said. “It shows us that there are a large number of candidate genes that can be examined to assess disease risk in vapers.”