Urine cotinine underestimates exposure to the tobacco-derived lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in passive compared with active smokers

Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2795-800. doi: 10.1158/1055-9965.EPI-10-0497. Epub 2010 Aug 30.

Abstract

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.

Methods: Cotinine and NNAL were measured in the urine of 373 active smokers and 228 passive smokers.

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 × 10(3) versus 0.16 × 10(3), P < 0.0001).

Conclusions: Passive smoking is associated with a much higher ratio of NNAL/cotinine in the urine compared with active smoking.

Impact: Cotinine measurement leads to an underestimation of exposure to the carcinogen NNK from secondhand smoke when compared with active smoking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / urine*
  • Carcinogens / analysis
  • Carcinogens / metabolism
  • Chromatography, Liquid
  • Cotinine / urine*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitrosamines / metabolism
  • Nitrosamines / urine*
  • Pyridines / urine*
  • Smoking / urine*
  • Tandem Mass Spectrometry
  • Tobacco Smoke Pollution*

Substances

  • Biomarkers
  • Carcinogens
  • Nitrosamines
  • Pyridines
  • Tobacco Smoke Pollution
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol
  • Cotinine