The authors of a new paper in Cancer Research have published the surprising finding that cigarettes and e-cigarettes have some similar effects on DNA methylation that have been reported to lead to cancer.
Harm reduction might not truly reduce harm
It is well-known that cigarettes are dangerous, with an extensive list of long-term harms, most notably lung cancer. Cigarette smoking has been held responsible for 7.69 million deaths around the world in 2019 alone [1].
E-cigarettes, which have a more controlled list of chemicals, are widely touted as being safer, with one Public Health England report stating that they are “95% less harmful” than cigarette smoking [2]. However, judging their actual long-term harm is difficult because they are relatively new and many of their users are former smokers; the authors of this paper state that such a comprehensive study would need to run for decades.
Some previous biomarker studies have been conducted, but they were more focused on immediate damage rather than long-term harm. Some of them have reported that such dangers are similar [3], while others state that switching from cigarettes to e-cigarettes reduces risk [4]. These researchers, however, decided to focus on a biomarker that more accurately reflects long-term harm: epigenetic alterations. Previous work has been done in this area, but these researchers focused on several cell types rather than just one, including cells that are not directly exposed.
Multiple data sources
This study used data from FORECEE, a cancer study that used data from women aged 18 to 83. Cells were taken from the cervix, the breast, and the inside of the cheek. More data was taken from the SEE-Cigs study conducted among 18- to 35-year-olds. More methylation data was taken from the ESTHER study conducted in Germany among a broad group of participants.
Comparing the cellular methylation of e-cigarette users to that of smokers and nonsmokers yielded some surprising results. While hypomethylation of cellular sites that should have been methylated was more similar to that of nonsmokers, hypermethylation of sites that should not have been methylated was more similar to that of smokers. This was somewhat apparent in far-away cells that are not directly exposed to e-cigarette vapor, but it was strongly apparent in the cells that are directly exposed to it.
Smokeless tobacco use had somewhat different patterns: sites on epithelial cells had more hypomethylation than that of smokers, but immune cells’ hypomethylation was indistingushable from that of nonsmokers. Hypermethylation was close to that of smokers in cells exposed to it. These findings are unsurprising in light of how smokeless tobacco is used.
This specific hypermethylation, the researchers note, is strongly associated with lung and cervical cancer. The epigenetic sites in question are associated with cellular growth and DNA damage response. While some cells, such as immune cells, appear to recover after people quit smoking [5], other research has suggested that it affects stem cells [6] – meaning that, without a thorough and currently unavailable intervention, the problem will never go away.
Smoking is a very good way to shorten lifespan, and these findings suggest that e-cigarette use, while potentially less harmful than smoking, is not beneficial either.
Literature
[1] Reitsma, M. B., Kendrick, P. J., Ababneh, E., Abbafati, C., Abbasi-Kangevari, M., Abdoli, A., … & Gorini, G. (2021). Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019. The Lancet, 397(10292), 2337-2360.
[2] McNeil, A., Brose, L. S., Calder, R., Hitchman, S. C., Hajek, P., & McRobbie, H. (2015). E-cigarettes: an evidence update. A report commissioned by Public Health England. Public Health England, 111, 14-15.
[3] Singh, K. P., Lawyer, G., Muthumalage, T., Maremanda, K. P., Khan, N. A., McDonough, S. R., … & Rahman, I. (2019). Systemic biomarkers in electronic cigarette users: implications for noninvasive assessment of vaping-associated pulmonary injuries. ERJ open research, 5(4).
[4] Polosa, R., Morjaria, J. B., Prosperini, U., Busà, B., Pennisi, A., Malerba, M., … & Caponnetto, P. (2020). COPD smokers who switched to e-cigarettes: health outcomes at 5-year follow up. Therapeutic Advances in Chronic Disease, 11, 2040622320961617.
[5] Yoshida, K., Gowers, K. H., Lee-Six, H., Chandrasekharan, D. P., Coorens, T., Maughan, E. F., … & Campbell, P. J. (2020). Tobacco smoking and somatic mutations in human bronchial epithelium. Nature, 578(7794), 266-272.
[6] Guida, F., Sandanger, T. M., Castagné, R., Campanella, G., Polidoro, S., Palli, D., … & Chadeau-Hyam, M. (2015). Dynamics of smoking-induced genome-wide methylation changes with time since smoking cessation. Human molecular genetics, 24(8), 2349-2359.
