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Direct link between smoking and developing lung cancer in humans

"Our finding identifies one of the direct links to lung cancer," Yuan said. "Tobacco smoke contains at least 60 established carcinogens and the more we can identify them, the better we will be able to accurately predict a smoker's risk.

Researchers at the Masonic Cancer Center, University of Minnesota have discovered a direct link between a cancer-causing compound in tobacco and the development of lung cancer in some smokers. This is the first time a direct link between smoking and lung cancer in humans has been identified.

"Although smoking is the most important causal factor for lung cancer, it has not been a very accurate predictor of risk," said Jian-Min Yuan, M.D., Ph.D., tobacco researcher at the Masonic Cancer Center and associate professor of public health, who led the team that made this discovery.

"We've known for a long time that smoking increases a person's risk for getting lung cancer, but we have not been able to clearly answer why one smoker would eventually develop lung cancer and another one would not. Now we know one definitive link," he said.

The findings were presented at the 2009 American Association for Cancer Research (AACR) annual meeting in Denver and published in the April issue of the journal Cancer Research

Yuan and his colleagues found the link to be NNAL, a cancer-causing compound originating from nicotine metabolites in cigarettes. This compound enters the body through cigarette smoking and is excreted in the urine. Previous research has shown NNAL to cause lung cancer in laboratory animals. Yuan thought the levels of NNAL and cotinine (another byproduct of nicotine) in the urine might be a way to predict a smoker's risk for lung cancer more accurately than self-reports of smoking. His theory proved correct - he and his team found that smokers with the highest levels of NNAL and cotinine in the urine had almost a nine-fold increased risk for developing lung cancer compared with smokers who had the lowest levels.

Yuan describes the two biomarkers - NNAL and cotinine - as the starting point of an individual-based, predictive model for determining a smoker's lifetime risk for lung cancer.

This research study involved data collected from 18,244 men enrolled in the Shanghai Cohort Study and 63,257 men and women in the Singapore Chinese Health Study. The researchers also conducted in-person interviews about cigarette smoking and dietary and lifestyle habits, and collected blood and urine samples from more than 50,000 participants in these groups. All of the participants were cancer-free when they enrolled in the study groups.

For this particular study, Yuan and his colleagues identified 246 smokers who developed lung cancer and 245 smokers who did not during the 10-year period following the interviews and collection of urine samples. They used the data and samples from these smokers to assess the link between NNAL and lung cancer.

The urine samples were divided into three groups according to levels of NNAL. The researchers found that compared with those with the lowest levels, smokers with a mid-range level of NNAL had a 43 percent increased risk of lung cancer and those at the highest level had more than double the risk. The researchers also factored in the number of cigarettes smoked per day, number of years of smoking, and levels of cotinine in the urine.

When the researchers also included the levels of cotinine in the urine, they found those with the highest levels of both NNAL and cotinine had an 8.5-fold increased risk of lung cancer compared with smokers with the lowest levels.

"Our goal [at the Masonic Cancer Center, University of Minnesota] in the next three to five years is to amass this information so that it can be used as a screening test to alert smokers of their risks," he noted.

Other researchers working with Yuan on this study were Woon-Puay Koh Koh, Sharon Murphy, Yunhua Fan, Renwei Wang, Steven Carmella, Shaomei Han, Latie Wickham, Tu-Tang Gao, Mmi Yu, and Stephen Hecht. These researchers are with the Masonic Cancer Center, University of Minnesota; National University of Singapore in Singapore, and Shanghai Cancer Institute in Shanghai, China.

Masonic Cancer Center, University of Minnesota 04 09

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