Background: We examined the nicotine metabolite ratio's (NMR) relationship with smoking intensity, nicotine dependence, and a broad array of biomarkers of exposure and biological effect in commercial cigarette smokers. Methods: Secondary analysis was conducted on two crosssectional samples of adult, daily smokers from Wave 1 (2013- 2014) of the Population Assessment of Tobacco Use and Health (PATH) Study and baseline data from a 2014-2017 randomized clinical trial. Data were restricted to participants of non-Hispanic, white race. The lowest quartile of NMR (<0.26) in the nationally representative PATH Study was used to distinguish slow from normal/fast nicotine metabolizers.NMRwas modeled continuously in secondary analysis. Results: Compared with slow metabolizers, normal/fast metabolizers had greater cigarettes per day and higher levels of total nicotine equivalents, tobacco-specific nitrosamines, volatile organic componds, and polycyclic aromatic hydrocarbons. A novel finding was higher levels of inflammatory biomarkers among normal/fast metabolizers versus slow metabolizers. With NMR modeled as a continuous measure, the associations between NMR and biomarkers of inflammation were not significant. Conclusions: The results are suggestive that normal/fast nicotine metabolizers may be at increased risk for tobacco-related disease due to being heavier smokers, having higher exposure to numerous toxicants and carcinogens, and having higher levels of inflammation when compared with slow metabolizers. Impact: This is the first documentation that NMR is not only associated with smoking exposure but also biomarkers of biological effects that are integral in the development of tobacco-related disease. Results provide support for NMR as a biomarker for understanding a smoker's exposure and potential risk for tobacco- related disease.
Bibliographical noteFunding Information:
Research reported in this publication was supported by National Institute on Drug Abuse of the NIH under award number U54 DA031659 (to D.K. Hatsukami
N.L. Benowitz is a consultant for Pfizer and Achieve Life Sciences and has provided expert testimony against tobacco companies. M. Kotlyar reports receiving a Global Research Award for Nicotine Dependence (GRAND) program funded by Pfizer. No potential conflicts of interest were disclosed by the other authors.
Research reported in this publication was supported by National Institute on Drug Abuse of the NIH under award number U54 DA031659 (to D.K. Hatsukami and E.C. Donny) and under award number K01DA043413 (to L.R. Pacek). Research reported in this publication was supported by NIH, National Research Service Award T32 DA007097 (to D.M. Carroll). Mass spectrometry for the RCT was conducted in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, supported in part by National Cancer Institute Cancer Center Support grant P30CA07759.
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