NEW YORK (Reuters Health) – High urinary levels of a carcinogen in tobacco may help predict risk of lung cancer in smokers, according to research reported at the American Association for Cancer Research (AACR) annual meeting in Denver.
NNAL, or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), is a tobacco-specific nitrosamine metabolite of NNK, or 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone). Both NNK and NNAL induce lung cancer in laboratory animals, but the effect in humans is less well understood.
"Findings of the present study directly link NNK exposure to lung cancer development in humans," report Dr. Jian-Min Yuan of the University of Minnesota School of Public Health in Minneapolis and colleagues in an AACR meeting abstract.
The investigators prospectively examined the risk of lung cancer in association with NNAL in prediagnostic urine samples obtained from cigarette smokers enrolled in two large population-based cohorts. Within these two cohorts, they conducted a nested case-control study involving 246 smokers who developed lung cancer and 245 smokers who did not develop lung cancer during a 10-year period following initial interview and collection of urine samples.
"Urinary levels of total NNAL were significantly associated with risk of lung cancer in a dose-dependent manner," the investigators report. Relative to the lowest tertile, lung cancer risk associated with the second and third tertiles of total NNAL was 1.43 and 2.11, respectively, after adjusting for self-reported smoking history and urinary levels of cotinine.
Smokers in the highest tertiles of urinary total NNAL and total cotinine had an 8.5-fold higher risk of lung cancer relative to smokers with comparable smoking history but having the lowest levels of urinary total NNAL and total cotinine.
In a statement from the meeting, Dr. Yuan noted that "a history of smoking has always been thought of as a predictor of lung cancer, but it is actually not very accurate. Smoking absolutely increases your risk, but why it does so in some people but not others is a big question."
Total NNAL and total cotinine in urine, Dr. Yuan and colleagues conclude, "are important predictors of lung cancer in smokers beyond the predictive indices of smoking intensity and duration. These two non-invasive biomarkers can serve as the starting point for an individual-based, predictive model for lung cancer risk in a smoker."