The tobacco-specific
nitrosamines N'-nitrosonornicotine (NNN) and
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are potent
carcinogens for the rat esophagus and lung, respectively. Consistent with the animal carcinogenicity data, we previously reported a remarkably strong association between prospectively measured urinary total NNN, a
biomarker of human NNN intake, and the risk of developing
esophageal cancer among smokers in the Shanghai Cohort Study. We also demonstrated that urinary total
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a
biomarker of exposure to the lung
carcinogen NNK, is strongly associated with the risk of lung, but not
esophageal cancer in smokers. In this study, we investigated the potential relationship between NNN intake and
lung cancer risk in the same cohort. The prospectively collected urine samples from
lung cancer cases and matching controls selected for this study, all current smokers, have been previously analyzed for total NNAL,
cotinine (a
biomarker of
nicotine intake) and
phenanthrene tetraol (PheT) (a
biomarker of exposure to
polycyclic aromatic hydrocarbons). Urinary levels of total NNN were not associated with the risk of
lung cancer: odds ratios (95% confidence intervals) associated with the second and third tertiles of total NNN, relative to the lowest tertile, were 0.82 (0.36-1.88) and 1.02 (0.39-2.89), respectively (p for trend = 0.959), after adjustment for self-reported smoking history, urinary
cotinine and PheT. The results of this study reaffirm the previously reported specificity of urinary total NNN and total NNAL as predictors of esophageal and
lung cancer risks, respectively, in smokers, and demonstrate remarkable coherence between rat target tissues of these
carcinogens and susceptibility to
cancer in smokers.