Urine Cotinine Underestimates Exposure to the Tobacco-Derived Lung Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone in Passive Compared with Active Smokers

<jats:title>Abstract</jats:title> <jats:p>Objectives: Cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are widely used biomarkers for tobacco-derived nicotine and the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively. The discrepancy between cotinine levels in relation to disease risk comparing active versus passive smoking suggests a nonlinear tobacco smoke dose-response and/or that cotinine is not providing an accurate measure of exposure to the toxic constituents of secondhand tobacco smoke.</jats:p> <jats:p>Methods: Cotinine and NNAL were measured in the urine of 373 active smokers and 228 passive smokers.</jats:p> <jats:p>Results: Average cotinine levels were 1,155 (interquartile range, 703-2,715) for active smokers and 1.82 (0.45-7.33) ng/mg creatinine for passive smokers. Average NNAL levels were 183 (103-393) and 5.19 (2.04-11.6) pg/mg creatinine, respectively. NNAL/cotinine ratio in urine was significantly higher for passive smokers when compared with active smokers (2.85 × 103 versus 0.16 × 103, P &lt; 0.0001).</jats:p> <jats:p>Conclusions: Passive smoking is associated with a much higher ratio of NNAL/cotinine in the urine compared with active smoking.</jats:p> <jats:p>Impact: Cotinine measurement leads to an underestimation of exposure to the carcinogen NNK from secondhand smoke when compared with active smoking. Cancer Epidemiol Biomarkers Prev; 19(11); 2795–800. ©2010 AACR.</jats:p>