Carcinogen Biomarkers in the Urine of Electronic Cigarette Users and Implications for the Development of Bladder Cancer: A Systematic Review

Eur Urol Oncol. 2021 Oct;4(5):766-783. doi: 10.1016/j.euo.2020.02.004. Epub 2020 Mar 16.


Context: Use of electronic cigarettes (e-cigarettes) has rapidly increased despite unclear longitudinal health effects. Once thought to be a safer alternative to tobacco smoke, it is possible that e-cigarettes expose the user to similar carcinogenic byproducts during the vaping process. These toxicants are metabolized and excreted in the urine, and may have oncogenic implications for bladder urothelium.

Objective: To characterize and summarize known urinary carcinogenic biomarkers in e-cigarette users as they relate to the risk of developing bladder cancer.

Evidence acquisition: A systematic literature search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and included PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). Relevant articles published in peer-reviewed journals, through January 2019, that reported on urinary biomarkers in e-cigarettes users were included. Parent compounds and urinary biomarkers were classified according to the International Agency for Research on Cancer Monographs on the Evaluation of Carcinogenic Risks to Humans and cross referenced using the Collaborative on Health and the Environment, Toxicant and Disease Database to determine a link to bladder cancer, grouped by strength of evidence.

Evidence synthesis: Our initial search identified 1385 articles, 22 of which met final inclusion criteria and were included for analysis. In summation, these studies described 40 different parent compounds and four metals found in the urine of e-cigarette users. Since each parent compound can be metabolized several different ways, 63 unique toxicant or carcinogenic metabolite biomarkers were identified. Compared with nonuser controls, e-cigarette users had higher concentrations of urinary biomarkers of several carcinogenic compounds linked to bladder cancer. The majority of studies were limited by heterogeneous reporting and a dearth of control individuals who had never smoked.

Conclusions: Biomarkers of carcinogens, several with a strong link to bladder cancer, are present in the urine of e-cigarette users. Long-term implications of urothelial exposure to these toxicants are unknown but concerning, given the similarities to tobacco smoke and its established relationship with bladder cancer. Further study on the urological safety of e-cigarettes is necessary.

Patient summary: Our review shows that several carcinogens that have a known link to bladder cancer are present in the urine of electronic cigarette (e-cigarette) users. Further study on the urological safety of e-cigarettes is necessary.

Keywords: Bladder cancer; Carcinogens; Electronic cigarette; Urinary biomarkers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Systematic Review

MeSH terms

  • Biomarkers
  • Carcinogens / analysis
  • Electronic Nicotine Delivery Systems*
  • Humans
  • Urinary Bladder Neoplasms* / diagnosis
  • Urinary Bladder Neoplasms* / epidemiology
  • Urinary Bladder Neoplasms* / etiology
  • Vaping*


  • Biomarkers
  • Carcinogens