Comparison of Bladder Carcinogens in the Urine of E-cigarette Users Versus Non E-cigarette Using Controls

Abstract

Electronic cigarette (EC) use is gaining popularity as a substitute for conventional smoking due to the perception and evidence it represents a safer alternative. In contrast to the common perception amongst users that ECs represent no risk initial studies have revealed a complex composition of e-cigarette liquids. Conventional cigarette smoking is a known risk factor for developing bladder cancer and prior reports raise concern some of those causative compounds may exist in EC liquids or vapor. Urine samples were collected from 13 e-cigarette using subjects and 10 non e-cigarette using controls. Five known bladder carcinogens that are either present in conventional cigarettes, products of combustion, or solvents believed to be used in some e-cigarette formulations were quantified by liquid chromatography – mass spectrometry (LC-MS). Analysis of e-cigarette user urine revealed the presence of two carcinogenic compounds, o-toluidine and 2-naphthylamine, at a mean 2.3 and 1.3 fold higher concentration (p-value of 0.0013 and 0.014 respectively). Many of these subjects (9/13) were long term nonsmokers (>12 months). Further study is needed to clarify the safety profile of e-cigarettes and their contribution to the development of bladder cancer given the greater concentration of carcinogenic aromatic amines in the urine of e-cigarette users.

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

“…Several studies found biomarkers indicative of combustible cigarette use in the e-cigarette-only groups, suggesting some study participants were undisclosed dual users or exposed to second-hand cigarette smoke [12,35]. An alternative explanation could also be that these biomarkers are truly present in e-cigarette users as well.…”

“…All 22 included studies were published since 2015. Participant mean/ median age was infrequently reported, but the median age of those reported was 36 yr [1,8,12,23,25,26,[31][32][33][34]. Study designs were primarily cross-sectional and longitudinal studies.…”

“…included a nonuser control group [1,12,[27][28][29]34], only a single study objectively confirmed a lack of combustible, ecigarette, or nicotine use through urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNAL) and salivary cotinine testing [1]. Five studies confirmed absence of noncombustible tobacco use by carbon monoxide levels (<10 ppm) in expired breath [7,8,24,26,35].…”

“…The European Public Health Association, US Food and Drug Administration, National Institutes of Health, and the Center for Disease Control all endorse that there are health risks associated with using e-cigarettes, but their safety profile has not been characterized definitively. Recent studies have shown that the health implications of ecigarette use may reach beyond the neurological impact of nicotine or the pulmonary effects due to inhalation to include the bladder [1,[10][11][12]. Specifically, toxic and carcinogenic parent compounds as well as biomarkers of their metabolized byproducts have been observed in the urine of e-cigarette users [1,12].…”

“…Recent studies have shown that the health implications of ecigarette use may reach beyond the neurological impact of nicotine or the pulmonary effects due to inhalation to include the bladder [1,[10][11][12]. Specifically, toxic and carcinogenic parent compounds as well as biomarkers of their metabolized byproducts have been observed in the urine of e-cigarette users [1,12]. Exposure of the bladder urothelium to these carcinogens may have implications for oncogenesis, particularly if the dose-dependent risk relationship seen in traditional tobacco-related bladder cancers is extrapolated to e-cigarettes [13].…”