A urine test may predict lung cancer risk

DENVER – A urine test that catches high levels of two tobacco-related compounds might reveal which cigarette smokers are most likely to develop lung cancer, researchers reported April 19 at a meeting of the American Association for Cancer Research. The study is the first to use biomarkers in urine to delineate lung cancer risk between large groups of smokers.

Researchers collected blood and urine samples from more than 18,000 people in Shanghai in the 1980s and 63,000 in Singapore in the 1990s, and monitored the health of these people for years afterward. In the new analysis, the scientists teamed with researchers from the University of Minnesota in Minneapolis to identify 246 smokers who had developed lung cancer and 245 smokers who hadn’t. These groups were matched in terms of age, gender and smoking history. All had provided a urine sample at the same time — before a cancer diagnosis had been made.

The urine samples obtained from smokers who later developed lung cancer were more than eight times as likely to have high levels of two tobacco-related compounds when compared with samples collected from the smokers who didn’t get lung cancer. The samples were gathered an average of five years before cancer was found, says study coauthor Jian-Min Yuan, an epidemiologist at the University of Minnesota.

The researchers measured a breakdown product of nitrosamine called NNAL, a known tobacco-related carcinogen, and cotinine, a marker of nicotine in the body.  

“The great thing about this study is they used a prospective design in which they collected urine from individuals in the past and waited until some [smokers] developed lung cancer, or didn’t,” says epidemiologist Christopher Amos of the University of Texas M.D. Anderson Cancer Center in Houston. “They clearly show that [nitrosamine] exposure is important,” he says.

High cotinine levels in the urine might serve as a proxy for an individual’s inability to clear out more dangerous tobacco compounds, Amos says.

Although cotinine itself isn’t a carcinogen, it is an excellent measure of how a smoker smokes, says Peter Shields, a physician and deputy director of the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, D.C. “Cotinine measurements show how deeply they are puffing and how long they are inhaling,” he says. Thus, analyzing both NNAL and cotinine levels gives researchers a better picture of the carcinogen circulating in the individual and the dose being extracted from cigarettes, he says.

Cost remains an issue. These tests cost $200 each, Yuan says. He hopes the measurements might be commercialized and drop into the $20 range. But ultimately, a combination of these sorts of biomarkers in blood or urine might pinpoint the smokers at highest risk, Yuan says.

Roughly 17 percent of male smokers and 11 percent of female smokers develop lung cancer. While identifying those at high risk of this malignancy is a laudable goal, Amos says, smokers need to remember that their habit also causes emphysema, contributes to heart disease and worsens the risk of many other ailments.