Dual cigarette and e-cig use increases human risk of lung cancer 40 times

As summarized in an earlier blog post, exposure to e-cigarette aerosol accelerates tumore growth and spread (metastasis) among established cancers. This effect is distinct from actually causing the cancer (i.e., carcinogenesis). Indeed, propylene glycol and vegetable glycerine (PG/VG), the primary solvents in e-liquid and which have been assumed to be inert are major causes of this tumor acceleration. These biological findings predict that people who smoke and also use e-cigarettes (dual users), would be at higher risk of cancer than people who just smoke.

Marissa Bittoni and colleagues at Ohio State recently published Vaping, Smoking and Lung Cancer Risk showing just that. As expected, they found daily smokers had 10 times the odds of having lung cancer compare to nonsmokers (OR=9.6, 95% CI=8.7-10.6) after adjusting for gender age and race. The odds of lung cancer exploded to 40 times among daily smokers who also vaped daily (OR=38.7, 95% CI=31.5-47.6) compared to nonsmokers.

In other words, adding e-cigarettes quadrupled the lung cancer risk of smoking cigarettes.

They drew this conclusion based on a case-control study in which they compared 4,975 people with recently diagnosed pathologically confirmed lung cancer to 27,294 controls without cancer that were matched by age, gender, race, and location of residence.

They also completed separate estimates for men and women, and for distinct histologic lung cancer cell types (pulmonary adenocarcinoma, squamous cell carcinoma, small cell and large cell carcinoma). They also did an analysis in which they adjusted for the effects of other diseases, including coronary artery disease and chronic obstructive pulmonary disease (COPD) as well as detailed smoking history (pack-years of smoking). In these separate analyses, they found that vaping increased the odds of lung cancer by 3-4 times above just smoking.

Because virtually all the e-cigarette users were also smokers, they could not estimate the lung cancer risk of just vaping. But, in terms of showing that vaping dramatically accelerates cancer caused by smoking, that is not a problem.

In addition, the fact that people have been smoking a lot longer than they were using e-cigarettes may not be the central factor since the e-cigarettes may be promoting a cancer that was established before the person started vaping.

Bittoni and colleagues highlight how this work shows that e-cigarettes are harm enhancing rather than harm reducing:

Results of the current study are in sharp contrast to reports that propose vaping as “harm reduction” compared to cigarette smoking. Our findings suggest that rather than creating a microenvironment that is less favorable for the growth and development of lung tumors, exposure to aerosolized e-liquid may in fact promote lung carcinogenesis. [citations dropped]

A particular implication of this work is that e-cigarettes should not be recommended as a reduced harm alternative or smoking cessation aid for people with cancer.

This work, in combination with recent insights into how e-cigarettes affect the tumor environment dramatically increases the importance of cancer as an outcome of e-cigarette use.

Here is the abstract:

Nicotine exposure through the use of electronic delivery systems (vaping) has been found to elevate the risk of certain conditions of the lungs, e.g., vaping associated lung injury, EVALI). However, the potential impact of vaping on lung cancer risk remains unexplored. We, therefore, examined the association of vaping and cigarette smoking with lung cancer risk in a case control study conducted in central Ohio. The study design compared 4,975 individuals with recently diagnosed pathologically confirmed carcinoma of the lung to 27,294 controls without cancer that were group matched at a 5:1 ratio to the cases by age, gender, race and location of residence. Odds ratios (OR) adjusted for gender, age and race revealed a fourfold higher risk of lung cancer among individuals who vaped in combination with chronic smoking (OR=58.9, 95% CI=47.3-70.5) versus individuals who only smoked cigarettes (OR=13.9, 95% CI=12.7-15.3, P<0.001). Further adjustment for prevalent comorbidities, chronic obstructive pulmonary disease and coronary artery disease, reduced the magnitude of the OR, but the risk for vaping and smoking (OR=38.7, 95% CI =31.5-47.6) remained fourfold higher than for smoking alone (OR=9.6, 95% CI= 8.7-10.6, P<0.001). This finding was consistent for men and women, with adjustment for pack-years of smoking, and for the main histological cell types of lung cancer. Our results suggest that the addition of vaping to smoking accelerates the risk of developing lung cancer.

Simple Summary: We compared cigarette smoking and use of electronic cigarettes (vaping) among 4,975 cases with lung cancer to 27,294 control subjects without cancer. The control subjects were from the same general location as the cases and had the same distribution of age, gender and race as the cases. We found that vaping combined with cigarette smoking was eight times more common in the cases with lung cancer than the control subjects, and the risk of developing lung cancer was four times higher among those who combined vaping and cigarette smoking than those who only smoked. These findings were consistent for men and women and for all major cell types of lung cancer. Our results suggest that vaping in combination with cigarette smoking accelerates the rate of developing lung cancer compared to smoking alone.

Here is the citation: Bittoni MA, Carbone DP, Harris RE. Vaping, Smoking and Lung Cancer Risk. J Oncol Res Ther. 2024;9(3):10229. doi: 10.29011/2574-710x.10229. Epub 2024 Jul 4. PMID: 39210964; PMCID: PMC11361252. It is available here.