The association of a tobacco-specific biomarker and cigarette consumption and its dependence on host characteristics

The tobacco-specific nitrosamine 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen, which can be characterized by urinary concentrations of the metabolite 4-(methylnitrosamino)-1-(3-pyridyl)butanol (NNAL) and its glucuronide. Using baseline data in current smokers from four clinical trials, we examine the associations of urinary cotinine with CPD and of total NNAL with cotinine and the modification of these associations by several host factors. There was a linear relationship between ln(cotinine) and ln(CPD) within categories of the Fagerstrom Test of Nicotine Dependence and of age. The increasing trend was significantly smaller for subjects with high and very high nicotine addiction and for older subjects and larger in females than males. The regression of In(total NNAL/cotinine) on In(cotinine) declined linearly, suggesting reduced NNK uptake per unit cotinine with increasing cotinine. The decline in trend was greater in subjects with increased CPD, with greater nicotine addiction, and at older ages and was smaller in females, although gender differences were small. Variations in the ratio with host characteristics were generally similar to a recent epidemiologic analysis of effect modification of the association between lung cancer and cigarette smoking.