ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2023
Impact of Genetic Variants in the Nicotine Metabolism Pathway on Nicotine Metabolite Levels in Smokers.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Genetic Basis of Tobacco Use Disorder.Genes · 2026Review
- Nicotine metabolites generate craniofacial defects that are worsened by ethanol exposure.PNAS nexus · 2026Article
- Au@Ag spiny sphere-based SERS for the ultrasensitive and rapid detection of nicotine in mainstream cigarette smoke.Mikrochimica acta · 2026Article
- Brain Cytochrome P450: Navigating Neurological Health and Metabolic Regulation.Journal of xenobiotics · 2025Review
- Racial/ethnic differences in the acute effects of reduced nicotine content cigarettes among adolescents who smoke.Addictive behaviors · 2025Article
- Nicotine Metabolism-Related Genetic Polymorphisms Associated with Smoking Cessation in Korean Men: A Candidate Gene Association Study in a Korean Cohort.Lifestyle genomics · 2025Article
- Effect of very low nicotine content cigarettes on smoking behavior in Chinese smokers with genotype-stratified nicotine metabolism rates.Frontiers in psychiatry · 2025Article
- Biochemical and genetic biomarkers associated with nicotine dependence in Mexican smokers.Pharmacology research & perspectives · 2023Article
- Inhibition of Nicotine Metabolism by Cannabidiol (CBD) and 7-Hydroxycannabidiol (7-OH-CBD).Chemical research in toxicology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundNicotine metabolism is a major factor in nicotine dependence, with approximately 70% to 80% of nicotine metabolized to cotinine in Caucasians. Cotinine formation is catalyzed primarily by CYP2A6, which also converts cotinine to trans-3'-hydroxycotinine (3HC). The goal of the present study was to examine the effects of CYP2A6 deficiency on nicotine metabolism profiles in vivo and the importance of genetic variants in nicotine-metabolizing enzyme genes on urinary nicotine metabolites levels.
methodsUrine samples from 722 smokers who participated in the Singapore Chinese Health Study were analyzed using UPLC-MS/MS to detect nicotine and eight of its urinary metabolites, and a total of 58 variants in 12 genes involved in nicotine metabolism were investigated in 475 of these subjects with informative genotyping data.
resultsUrine samples stratified by the ratio of 3HC/cotinine exhibited a 7-fold increase in nicotine-N'-oxide, a 6-fold increase in nicotine-Glucuronide (Gluc), and a 5-fold decrease in 3HC-Gluc when comparing the lower versus upper 3HC/cotinine ventiles. Significant (P < 0.0001) associations were observed between functional metabolizing enzyme genotypes and levels of various urinary nicotine metabolites, including CYP2A6 genotype and levels of nicotine, nicotine-Gluc, nicotine-N'-oxide and 3HC, UGT2B10 genotype and levels of cotinine, nicotine-Gluc and cotinine-Gluc, UGT2B17 genotype and levels of 3HC-Gluc, FMO3 genotype and levels of nicotine-N'-oxide, and CYP2B6 genotype and levels of nicotine-N'-oxide and 4-hydroxy-4-(3-pyridyl)-butanoic acid.
conclusionsThese data suggest that several pathways are important in nicotine metabolism. IMPACT: Genotype differences in several nicotine-metabolizing enzyme pathways may potentially lead to differences in nicotine dependence and smoking behavior and cessation.
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