Researchers are a step closer to developing a simple urine test to identify smokers at high risk of developing lung cancer.
Although the test is still years away, the hope is to spot high-risk people earlier, when there’s still time to prevent or treat the cancer, says Jian-Min Yuan, MD, associate professor of cancer epidemiology at the University of Minnesota.
Early identification will give doctors a chance to step up smoking cessation and screening efforts, he tells WebMD.
“It might motivate smokers who are having trouble quitting” to finally kick the habit, Yuan says.
If that fails, “We can at least have them come in for lung cancer screening every six months,” he says. That way, doctors can catch cancer earlier, when there’s a higher chance it can be treated successfully with surgery, radiation, and/or chemotherapy.
The findings were presented at the annual meeting of the American Association for Cancer Research.

Smoking Causes Lung Cancer
Lung cancer is the leading cancer killer, claiming the lives of more than 160,000 Americans last year, according to the American Cancer Society.
Smoking tobacco is the major risk factor for lung cancer. In the United States, about 90% of lung cancer deaths in men and nearly 80% of lung cancer deaths in women are from smoking, according to the CDC. People who smoke are 10 to 20 times more likely to get lung cancer or die from lung cancer than people who do not smoke.
But not every smoker develops lung cancer, and there is no way to predict exactly who will develop the disease, says Peter G. Shields, MD, deputy director of the Lombardi Comprehensive Cancer Center in Washington, D.C.
“We all know that the more you smoke, the higher your risk. But only about one in 10 heavy smokers gets lung cancer,” he tells WebMD.
“It’s really remarkable that we have tests for cholesterol and so on, but we don’t have a blood or urine test for smoking,” Shields says.

Developing a Urine Test
In an effort to develop such a test, Yuan and colleagues culled data from two large studies that began about 20 years ago. One, called the Shanghai Cohort Study, involved more than 18,000 men in Shanghai, China. The other, the Singapore Chinese Health Study, included 63,257 men and women of Chinese descent.
At the time of enrollment, urine and blood samples were collected from all the participants and frozen for future use. They were also asked to answer a battery of questions, including whether they smoked, how much they smoked, and for how long they smoked.
For the new analysis, the researchers focused on 245 smokers in the studies who developed lung cancer and 245 smokers who didn’t get cancer.
Then they thawed their urine samples and measured levels of NNAL, a byproduct of one of the most potent tobacco lung carcinogens identified to date.
“When you smoke, you suck in about 60 carcinogens. One of the most potent, called NNK, breaks down and becomes NNAL in the body,” Yuan says.
NNAL has been shown to induce lung cancer in laboratory animals, but the effect in humans had not yet been studied, he says.
Then the smokers were divided into three groups based on their levels of NNAL in the urine.
Compared with those with the lowest levels, people with a mid-range level of NNAL had a 43% increased risk of lung cancer. Those with the highest levels had more than twice the risk of lung cancer.
Then the researchers measured a byproduct of nicotine, called cotinine, in the urine.
Smokers with the highest levels of both cotinine and NNAL had an 8.5-fold increase in the risk of lung cancer compared with smokers who had the lowest levels.
The findings held true even after taking into account the number of cigarettes smoked per day, the number of years of smoking, and other factors.
The next step is to measure another tobacco-carcinogen byproduct called PAH in the participants’ urine and look at whether high levels of all three chemicals even further raises risk, Yuan says.
“The idea is to build up a risk model that incorporates many of these biomarkers as well as smoking history, so we can best identify which smokers will eventually develop lung cancer,” he says.


American Association for Cancer Research 100th Annual Meeting, Denver, April 18-22, 2009.
Jian-Min Yuan, MD, associate professor, cancer epidemiology, University of Minnesota.
Peter G. Shields, MD, deputy director, Lombardi Comprehensive Cancer Center, Washington, D.C.


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