Metabolites of a tobacco-specific lung carcinogen in nonsmoking women exposed to environmental tobacco smoke

Background: Environmental tobacco smoke (ETS) is associated with lung cance r in nonsmokers, Most epidemiologic studies find a higher risk for lung can cer in nonsmoking women married to smokers than in those married to nonsmok ers. We measured metabolites of a tobacco-specific lung carcinogen in urine from healthy, nonsmoking women exposed to ETS, Methods: We recruited women and their partners through advertisements, Couples completed questionnaire s on smoking history and demographics, and both partners provided 100 mL of urine; 23 women had male partners who smoked in the home (i.e., exposed wo men), and 22 women had male partners who did not smoke (i.e., unexposed wom en). Urine samples were analyzed for nicotine, for cotinine, for 4-(methyln itrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc), as well as for creatinine. NNAL and NNAL-Gluc are metabolites of the tobac co-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), Unpaired Student's t tests were conducted on log-transformed values, All statistical tests are two-sided. Results: Urinary levels of nicotine, cotinine, NNAL, and NNAL-Gluc were statistically significantly higher in ex posed women than in unexposed women, Geometric means for these compounds in exposed versus unexposed women, respectively, were as follows: nicotine, 0 .050 nmol/mg of creatinine (95% confidence interval [CI] = 0.033 to 0.076) versus 0.008 nmol/mg of creatinine (95% CI = 0.004 to 0.014); cotinine, 0.0 37 nmol/mg of creatinine (95% CI = 0.022 to 0.061) versus 0.007 nmol/mg of creatinine (95% CI = 0.004 to 0.011); NNAL, 0.013 pmol/mg of creatinine (95 % CI = 0.007 to 0.024) versus 0.004 pmol/mg of creatinine (95% CI = 0.002 t o 0.007); and NNAL-Gluc, 0.027 pmol/ mg of creatinine (95% CI = 0.016 to 0. 045) versus 0.001 pmol/mg of creatinine (95% CI = 0.003 to 0.006). Conclusi ons: Nonsmoking women exposed to ETS take up and metabolize the tobacco-spe cific lung carcinogen NNK, which could increase their risk of lung cancer. Within couples, the NNAL plus NNAL-Gluc level in exposed women compared wit h that of their smoking partners averaged 5.6%. Notably, epidemiologic stud ies have estimated the excess risk for lung cancer in nonsmoking women expo sed to ETS as 1%-2% of that in smokers.