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Title: Relationships between the Nicotine Metabolite Ratio and a Panel of Exposure and Effect Biomarkers: Findings from Two Studies of U.S. Commercial Cigarette Smokers.

Authors: Carroll, Dana M; Murphy, Sharon E; Benowitz, Neal L; Strasser, Andrew A; Kotlyar, Michael; Hecht, Stephen S; Carmella, Steve G; McClernon, Francis J; Pacek, Lauren R; Dermody, Sarah S; Vandrey, Ryan G; Donny, Eric C; Hatsukami, Dorothy K

Published In Cancer Epidemiol Biomarkers Prev, (2020 04)

Abstract: 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 cross-sectional 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. NMR was 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.

PubMed ID: 32051195 Exiting the NIEHS site

MeSH Terms: Adult; Biomarkers/blood; Biomarkers/metabolism; Biomarkers/urine; Cigarette Smoking/blood*; Cigarette Smoking/immunology; Cigarette Smoking/metabolism; Cigarette Smoking/urine; Cotinine/analogs & derivatives*; Cotinine/blood; Cotinine/metabolism; Cotinine/urine; Cross-Sectional Studies; Datasets as Topic; Female; Humans; Inflammation/blood; Inflammation/diagnosis; Inflammation/immunology; Inflammation/urine; Longitudinal Studies; Male; Middle Aged; Nicotine/blood*; Nicotine/metabolism; Nicotine/urine; Randomized Controlled Trials as Topic; Self Report/statistics & numerical data; Severity of Illness Index; Smokers/statistics & numerical data; Tobacco Use Disorder/blood; Tobacco Use Disorder/diagnosis*; Tobacco Use Disorder/immunology; Tobacco Use Disorder/urine; United States

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