Carcinogens Found in Urine of e-Cigarette Users

Nick Mulcahy

May 15, 2017

BOSTON — The widely held belief that e-cigarettes do not pose a cancer threat may be wishful thinking, according to the results of a new pilot study that focuses on their potential impact on bladder cancer.

The small study showed that two known carcinogens, otoluidine and 2-naphthylamine, were found in the urine of e-cigarette users but not in nonusers.

"That's concerning because we know there are people who genetically susceptible to developing bladder cancer," said lead study author, Thomas Fuller, MD, a urologist at the University of Pittsburgh in Pennsylvania.

Traditional cigarette smoking is a major risk factor for bladder cancer. e-Cigarettes have gained popularity, in part because they are perceived as a safer alternative, he explained.

"No level of exposure to these carcinogens is without risk," Dr Fuller told Medscape Medical News after he discussed the study at press conference today at the American Urological Association (AUA) 2017 Annual Meeting. However, he also admitted that the clinical implication of the findings about otoluidine and 2-naphthylamine is unknown.

Previous studies of traditional cigarette smokers have identified otoluidine and 2-naphthylamine as the two most carcinogenic molecules for the bladder, Dr Fuller said.

In the new study, 12 of the 13 e-cigarette users whose urine was analyzed had both otoluidine and 2-naphthylamine detected (limits of detection were 100 ng/mL and 10 ng/mL, respectively). None of the 10 controls were positive for the compounds.

Specifically, among e-cigarette users, there were 2.3-fold mean concentration level increases for otoluidine (P = .0013) and a 1.3-fold increase for 2-naphthylamine (P = .014) compared with controls.

Notably, all study participants, when interviewed by investigators, said that e-cigarettes were "safe."

Dr Fuller also commented that, among traditional cigarette smokers, the urine levels of these molecules would be "greater."

The investigators examined study participants' urine for three other carcinogens — benz(a)anthracene, benzo(a)pyrene, and 1- hydroxypyrene — but found no significant findings for these molecules.

The study's e-cigarettes users were also ex-smokers of traditional cigarettes; they had a median of 20 years of use. Importantly, they had quit traditional cigarettes for a median of 15 months before the current study. And they had been using e-cigarettes for a median of 26 months. So, there was a period in the past in which most participants overlapped use of both forms of smoking.

Press conference moderator, Sam Chang, MD, a urologist from Vanderbilt University in Nashville, Tennessee, wondered whether there was a correlation between frequency of e-cigarette use and urine levels of the carcinogens.

Dr Fuller revealed that they could not assess that because most of the study participants (84.6%) used e-cigarettes more than 28 times a week (about four times a day). The study questionnaire had assumed that this four-times-a-day frequency would be the upper limit of use. But it turned out to be a lower limit. "We underestimated how often people are using these e-cigarettes," he said.

Bladder Cancer Research Is Just Starting

Dr Chang believes the study, despite its small size, is an important step in understanding e-cigarettes and their potential bladder cancer threat.

The new study reveals that problematic chemical molecules are "processed, end up in the urine, which end up sitting in the bladder, which inevitably will have some impact on the likelihood of the development of cancer," he said. 

Dr Chang also repeated the importance of a slide shown by Dr Fuller depicting the skyrocketing e-cigarette use among middle school and high school students from 2013 to 2015, with a jump in users from about 8% to 25% of all students over that time.

As a father of three school-aged daughters, Dr Chang said the threat of e-cigarette use in their age groups is "scary, scary."

Dr Fuller acknowledged that research into e-cigarettes and their effect on the bladder lags behind research into their effect on the lungs.

"Maybe as a community, we [urologists] bought into the idea that this was going to be a much safer alternative because there is no combustion," he said.

Dr Fuller said that a next step for research is that the new results need confirmation in a larger study. And more carcinogens must be examined. The current study looked at only five molecules that are considered carcinogenic.

The new results conflict somewhat with the message from other recent research from the United Kingdom that suggests e-cigarettes are largely safe and certainly an improvement over traditional cigarettes.

As reported by Medscape Medical News, former smokers who only used e-cigarettes or nicotine replacement therapy were substantially less likely to be exposed to carcinogens and toxins than those who continue to smoke, according to a cross-sectional study that looked at urine and blood samples.

Dr Fuller and Dr Chang have disclosed no relevant financial relationships.

American Urological Association (AUA) 2017 Annual Meeting. Abstract MP88-14. Presented May 15, 2017.

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