Individuals who switch from conventional cigarettes to e-cigarettes rather than quitting nicotine use altogether remain at a higher risk of developing and dying from lung cancer, according to a large South Korean study published in Nature Medicine.

The analysis, which included more than 4.5 million participants, adds to growing evidence that although e-cigarettes may expose users to fewer harmful substances than combustible tobacco products, they are not risk-free and may not provide the same health benefits as complete smoking cessation.

Limited Evidence

In some countries, including the UK, e-cigarettes are used as smoking cessation aids because they are generally considered less harmful than conventional cigarettes and may help individuals quit smoking.

However, increasing evidence suggests that e-cigarettes may also cause health risks, including cancer. Until now, long-term evidence evaluating the health effects of switching from conventional cigarettes to e-cigarettes has been limited.

Yeon Wook Kim, MD, of the Department of Internal Medicine at Seoul National University College of Medicine in Seoul, South Korea, and colleagues analyzed data from the Korean National Health Screening Program, a preventive healthcare system available to insured individuals who participate in routine health examinations.

Higher Risk

The researchers found that individuals who switched from conventional cigarettes to e-cigarettes had an approximately 50% higher risk for lung cancer and a two-fold higher risk for lung cancer mortality than those who quit smoking completely.

The association was particularly strong among individuals at the highest risk for lung cancer, including those aged 50-80 years with at least 20 pack-years of exposure to smoking.

Best Option

Speaking with Science Media Center, Daniel Kotz, MD, professor of Addiction Research and Clinical Epidemiology from the Institute of General Practice, Addiction Research and Clinical Epidemiology Unit, Medical Faculty of the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; said, “The study’s findings suggest that the risk of lung cancer can be reduced much more effectively if people refrain from using e-cigarettes in addition to smoking tobacco.”

“Since e-cigarettes, unlike conventional cigarettes, do not produce combustion byproducts and thus result in the inhalation of significantly fewer harmful substances, they are less harmful than conventional cigarettes, but they are not harmless,” said Ute Mons, PhD, head of the Department of Primary Cancer Prevention at the German Cancer Research Center in Heidelberg, Germany.

In her view, the findings support the recommendations in the German tobacco cessation guidelines.

“Quitting smoking completely is the best option and can most reliably be achieved with behavioral therapy support, supplemented, if necessary, by nicotine replacement products or smoking cessation medications,” she said.

Mons added that e-cigarettes should be considered only when guidelines recommended smoking cessation approaches have been unsuccessful or declined by the patient. In such cases, they should only be used temporarily, followed by gradual tapering of nicotine exposure.

Increased Risk

Natascha Sommer, MD, head of the Pulmonology Outpatient Clinic and senior physician in Pulmonology and Intensive Care Medicine from Justus Liebig University Giessen, Giessen, Germany noted that the cohort study is among the first to demonstrate an increased risk for lung cancer among individuals who use e-cigarettes after stopping conventional smoking.

She cautioned that the study design could not establish causality between e-cigarette use and lung cancer. However, she noted that the large sample size, relatively long follow-up period, adjustment for potential confounding factors, and prospective outcome collection strengthened the validity of the observed associations.

Questioning Harm Reduction

“Increased risk of developing lung cancer and a 100% increased risk for mortality from a lung cancer-associated death was shown when switching to e-cigarette smoking after termination of tobacco smoking was made compared with complete smoking abstinence,” Sommer said.

She added that these findings are biologically plausible. Preclinical studies have demonstrated the carcinogenic effects of nicotine.

“Nicotine must therefore be considered as a carcinogenic cell poison in any delivery form,” Sommer said.

Martin Widschwendter, MD, PhD, director of The Daffodil Centre at the University of Sydney, Sydney, Australia, noted based on his earlier research showing that both conventional cigarettes and e-cigarettes induce cell type specific DNA methylation changes in epithelial cells. These alterations are associated with carcinogenesis and may predict future lung cancer, including lung cancer among e-cigarette users with relatively limited smoking histories.

From a prevention perspective, the findings raise concerns about the perception of e-cigarettes as a safer alternative, according to Reiner Hanewinkel, PhD, director of the Institute for Therapy and Health Research in Kiel, Germany.

“When one considers the results of the study with a sharpened, prevention-oriented view, the potential dangers of e-cigarettes become clearly evident,” Hanewinkel said.

He argued that the study findings debunked the ‘harm reduction’ illusion: The tobacco and e-cigarette industry advertises massively that e-cigarettes are a ‘healthier’ alternative. This study exposes this as a dangerous fallacy for the lungs.

“Second, a prevention-policy setback is shown here: From the perspective of tobacco control, e-cigarettes often prevent true, complete quitting. Instead of completely overcoming nicotine dependence, consumers merely shift their behavior to another product. The study results suggest that this ‘gentle switch’ at least strongly breaks the oncological recovery process of the lung after smoking cessation,” he emphasized.

“The study shows that the only legitimate and safe goal of tobacco prevention must be complete pollutant and nicotine abstinence.”

Policy Implications

“There are in Germany proven effective and safe methods to quit tobacco smoking. e-cigarettes and other nicotine products, such as heated tobacco or nicotine pouches, do not belong to them,” Kotz said.

Medically recommended include digital health applications, telephone counselling, cessation courses, and nicotine replacement therapy or medications that alleviate withdrawal symptoms. These methods help with complete and permanent tobacco and nicotine abstinence, whereby the risk for diseases such as lung cancer can be strongly reduced.

Kotz also argued that stronger measures are needed to reduce tobacco and nicotine use, particularly in young individuals.

“Overall, Germany can and must do more to reduce the consumption of tobacco and nicotine in the population so that diseases such as lung cancer do not arise at all. Particularly, our youth must be protected, who are targeted and made dependent by nicotine products of the industry,” he said.

Sommer added that the “results of the current study therefore appear unsurprising against this background and offer further arguments for the restriction of e-cigarette smoking by similar measures as successfully with conventional tobacco cigarettes, for example location-bound smoking bans and higher taxes, as well as extensive education and cessation measures. Particularly as a means for tobacco cessation, e-cigarettes prove on the basis of these study results as unsuitable.”

“Against the background of recently published numbers on increasing e-cigarette smoking by children and adolescents, this study should constitute a wake-up call not to trivialize the dangers of e-cigarettes and to consistently implement access restrictions for children and adolescents. This study provides a basis for rethinking, and consumption of nicotine in any form is to be regarded as highly health-damaging. Despite the limitations of this study, there is now numerous evidence that a societal experiment with e-cigarettes will lead to a health-unacceptably burden on users and cost increase in the health system through long-term effects,” she concluded.

Study Limitations

This study had several limitations. Smoking status was based on self-reported information, and the analysis did not account for differences among e-cigarette devices or product characteristics.

In addition, the maximum follow-up period of 6 years may be relatively short for evaluating long-term lung cancer incidence and mortality. The number of lung cancer cases in some e-cigarette user subgroups was also small, limiting the reliability of the subgroup analyses.

This story was translated from Medscape’s German edition.