Inflammatory and Carcinogenic Biomarker Signatures in E-Cigarette Users: A Comprehensive Meta-Analysis of ∼24,000 Adults

Abstract

Objectives: This meta-analysis examined the association between electronic cigarette (e-cig) use and biomarkers related to lung inflammation and carcinogenesis. Methods: A systematic review of PubMed, Scopus, Web of Science, EMBASE, and Cochrane Library (2014–April 2024) identified 16 studies including 24,079 adults. Biomarkers from urine, saliva, and plasma—cotinine, NNAL, NAT, and interleukins—were analyzed using one-way ANOVA and Tukey’s post-hoc tests. The GRADE framework assessed evidence certainty and risk of bias. Results: Among participants, 27.2% were smokers, 2.7% e-cig users, 66.0% non-smokers, and 4.1% dual users. E-cig users showed higher salivary cotinine than non-smokers (p = 0.033) but not smokers (p = 0.99). NNAL was significantly elevated in smokers (p = 0.035). E-cig users had increased inflammatory markers (IL-6, TNF-α) compared with non-smokers but lower than smokers. Carcinogenic biomarkers were present in e-cig users at reduced concentrations versus smokers. GRADE indicated low to high certainty with no or moderate bias. Conclusion: E-cigarette use is associated with biomarker alterations indicating inflammation and potential carcinogenesis, paralleling some effects of traditional smoking. Standardized longitudinal studies are needed to establish causality and long-term risks.