Biomarkers of Carcinogens Linked to Bladder Cancer in Urine of E-Cigarette Users

Biomarkers of carcinogens, including several with a strong link to bladder cancer, were found to be present in the urine of e-cigarette users, according to a study published in European Urology Oncology.¹

Though the long-term implications of urothelial exposure to these toxicants is currently unknown, it remains concerning given the similarities to tobacco smoke and its established relationship with bladder cancer. Given these findings, researchers indicated that further study of the urological safety of e-cigarettes is necessary. 

“Although there is no definitive case yet linking bladder cancer to vaping, it may be reasonable to suspect that decades down the road after exposure to these byproducts, people who vape may be at risk of developing bladder cancer,” Marc Bjurlin, DO, MSc, from the University of North Carolina Lineberger Comprehensive Cancer Center, said in a press release.²

Researchers performed a systematic literature search 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). The initial search identified 1,385 articles, 22 of which met the final inclusion criteria and were included in the analysis.

Overall, the literature described 40 different parent compounds and 4 metals found in the urine of e-cigarette users. Since each parent compound has the ability to be metabolized several different ways, 63 unique toxicant or carcinogenic metabolite biomarkers were identified. 

When compared with nonuser controls, e-cigarette users had higher concentrations of urinary biomarkers of several carcinogenic compounds linked to bladder cancer. However, the majority of studies were limited by heterogenous reporting and a dearth of control individuals who had never smoked. 

“This finding shows us that people who vape will be exposed to a variety of different carcinogens,” said Bjurlin. “People who have decades of exposure to these carcinogens from vaping map be at risk for developing malignancies, especially bladder cancer.”

Notably, there were several limitations to the study, such as researchers not knowing the levels of all of the cancer-causing substances in the urine of users from the studies. Additionally, some studies included individuals who were “dual users,” or those who both smoked and vaped e-cigarettes. There were also cases when users smoked cigarettes and switched to smoking e-cigarettes.

“The study population was quite heterogeneous, meaning that often studies looked at dual users, meaning those who used e-cigarettes and combustible cigarettes,” said Bjurlin. “That made it difficult to assess whether the carcinogen found in the urine was actually from the e-cigarette use or from the cigarette use.” 

Bjurlin indicated that further research is necessary, and he specifically wants to determine the threshold of exposure to carcinogens that would lead to the development of bladder cancer or other types of cancer. He intends to lead to a study that will evaluate carcinogens in the urine of e-cigarette users, smokers, and non-users.

“Moving forward, the scientific community should approach the study of e-cigarette-related urinary exposures systematically,” the authors wrote. “It will be important to assess the presence of carcinogens and biomarkers in the urine of exclusive e-cigarette users, as it relates to frequency and intensity of use.”

Moreover, although currently based on limited evidence, clinicians should adhere to the side of caution when advising patients about the use of e-cigarettes according to the researchers. Ongoing popularity of their use and the continued evolution of e-cigarette devices requires honest discussion with patients about the relative possible risks and benefits to consider, including the possibility for developing bladder cancer. 

References:

1. Bjurlin MA, Matulewicz RS, Roberts TR, et al. Carcinogen Biomarkers in the Urine of Electronic Cigarette Users and Implications for the Development of Bladder Cancer: A Systematic Review. European Urology Oncology. doi:10.1016/j.euo.2020.02.004.

2. E-cigarette users had substances linked to bladder cancer in urine [news release]. Chapel Hill, North Carolina. Published March 19, 2020. newswise.com/articles/e-cigarette-users-had-substances-linked-to-bladder-cancer-in-urine?sc=mwhr&xy=10021790. Accessed March 24, 2020.