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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Carroll, DM; Murphy, SE; Benowitz, NL; Strasser, AA; Kotlyar, M; Hecht, SS; Carmella, SG; McClernon, FJ; Pacek, LR; Dermody, SS; Vandrey, RG; Donny, EC; Hatsukami, DK

Published Date

  • April 2020

Published In

Volume / Issue

  • 29 / 4

Start / End Page

  • 871 - 879

PubMed ID

  • 32051195

Pubmed Central ID

  • PMC7437528

Electronic International Standard Serial Number (EISSN)

  • 1538-7755

Digital Object Identifier (DOI)

  • 10.1158/1055-9965.EPI-19-0644


  • eng

Conference Location

  • United States