Tobacco-constituent
biomarkers are metabolites of specific compounds present in tobacco or tobacco
smoke. Highly reliable analytic methods, based mainly on mass spectrometry, have been developed for quantitation of these
biomarkers in both urine and blood specimens. There is substantial interindividual variation in smoking-related
lung cancer risk that is determined in part by individual variability in the uptake and metabolism of tobacco
smoke carcinogens. Thus, by incorporating these
biomarkers in epidemiologic studies, we can potentially obtain a more valid and precise measure of in vivo
carcinogen dose than by using self-reported smoking history, ultimately improving the estimation of smoking-related
lung cancer risk. Indeed, we have demonstrated this by using a prospective study design comparing
biomarker levels in urine samples collected from smokers many years before their development of
cancer versus those in their smoking counterparts without a
cancer diagnosis. The following urinary metabolites were associated with
lung cancer risk, independent of smoking intensity and duration:
cotinine plus its
glucuronide, a
biomarker of
nicotine uptake;
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its
glucuronides (total NNAL), a
biomarker of the tobacco
carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); and r-1-,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), a
biomarker of
polycyclic aromatic hydrocarbons (PAH). These results provide several possible new directions for using tobacco
smoke-constituent
biomarkers in
lung cancer prevention, including improved
lung cancer risk assessment, intermediate outcome determination in prevention trials, and regulation of tobacco products.