ArticleCarcinogenesis2013
Alaska Native smokers and smokeless tobacco users with slower CYP2A6 activity have lower tobacco consumption, lower tobacco-specific nitrosamine exposure and lower tobacco-specific nitrosamine bioactivation.
Article in Carcinogenesis, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- Genome-wide association meta-analysis of nicotine metabolism and cigarette consumption measures in smokers of European descent.Molecular psychiatry · 2021Pooled it
- Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2.Scientific reports · 2016Pooled it
- Correlates of the nicotine metabolite ratio in Alaska Native people who smoke cigarettes.Experimental and clinical psychopharmacology · 2022Trial
- Nicotine Metabolite Ratio Is Associated With Lozenge Use But Not Quitting in Smokeless Tobacco Users.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2016Trial
- Known and novel sources of variability in the nicotine metabolite ratio in a large sample of treatment-seeking smokers.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2014Trial
- Association of CHRNA5-A3-B4 SNP rs2036527 with smoking cessation therapy response in African-American smokers.Clinical pharmacology and therapeutics · 2014Trial
- Estimating lung cancer risk from e-cigarettes and heated tobacco products: applications of a tool based on biomarkers of exposure and of potential harm.Harm reduction journal · 2025Article
- CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility.Cancer research · 2024Article
- Genomics and inclusion of Indigenous peoples in high income countries.Human genetics · 2023Review
- Exploring Potential for a Personalized Medicine Approach to Smoking Cessation With an American Indian Tribe.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2023Article
- Smoking Patterns Among Urban Alaska Native and American Indian Adults: The Alaska EARTH 10-Year Follow-up Study.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022Article
- Nicotine self-administration with menthol and audiovisual cue facilitates differential packaging of CYP2A6 and cytokines/chemokines in rat plasma extracellular vesicles.Scientific reports · 2021Article
- Pharmacogenomics of Nicotine Metabolism: Novel CYP2A6 and CYP2B6 Genetic Variation Patterns in Alaska Native and American Indian Populations.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2020Article
- Relationships between the Nicotine Metabolite Ratio and a Panel of Exposure and Effect Biomarkers: Findings from Two Studies of U.S. Commercial Cigarette Smokers.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- Association of CYP2A6 gene deletion with cancers in Japanese elderly: an autopsy study.BMC cancer · 2020Article
- The Multifarious Link between Cytochrome P450s and Cancer.Oxidative medicine and cellular longevity · 2020Review
- Social Media Intervention to Promote Smoking Treatment Utilization and Cessation Among Alaska Native People Who Smoke: Protocol for the Connecting Alaska Native People to Quit Smoking (CAN Quit) Pilot Study.JMIR research protocols · 2019Article
- Induction via Functional Protein Stabilization of Hepatic Cytochromes P450 upon gp78/Autocrine Motility Factor Receptor (AMFR) Ubiquitin E3-Ligase Genetic Ablation in Mice: Therapeutic and Toxicological Relevance.Molecular pharmacology · 2019Article
- The relationship between nicotine metabolism and nicotine and carcinogen exposure among American Indian commercial cigarette smokers and electronic nicotine delivery system users.Addictive behaviors · 2019Article
- Relationships Between Smoking Behaviors and Cotinine Levels Among Two American Indian Populations With Distinct Smoking Patterns.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2018Article
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 3 countries.
Funding
Abstract
Nicotine, the psychoactive ingredient in tobacco, is metabolically inactivated by CYP2A6 to cotinine. CYP2A6 also activates procarcinogenic tobacco-specific nitrosamines (TSNA). Genetic variation in CYP2A6 is known to alter smoking quantity and lung cancer risk in heavy smokers. Our objective was to investigate how CYP2A6 activity influences tobacco consumption and procarcinogen levels in light smokers and smokeless tobacco users. Cigarette smokers (n = 141), commercial smokeless tobacco users (n = 73) and iqmik users (n = 20) were recruited in a cross-sectional study of Alaska Native people. The participants' CYP2A6 activity was measured by both endophenotype and genotype, and their tobacco and procarcinogen exposure biomarker levels were also measured. Smokers, smokeless tobacco users and iqmik users with lower CYP2A6 activity had lower urinary total nicotine equivalents (TNE) and (methylnitrosamino)-1-(3)pyridyl-1-butanol (NNAL) levels (a biomarker of TSNA exposure). Levels of N-nitrosonornicotine (NNN), a TSNA metabolically bioactivated by CYP2A6, were higher in smokers with lower CYP2A6 activities. Light smokers and smokeless tobacco users with lower CYP2A6 activity reduce their tobacco consumption in ways (e.g. inhaling less deeply) that are not reflected by self-report indicators. Tobacco users with lower CYP2A6 activity are exposed to lower procarcinogen levels (lower NNAL levels) and have lower procarcinogen bioactivation (as indicated by the higher urinary NNN levels suggesting reduced clearance), which is consistent with a lower risk of developing smoking-related cancers. This study demonstrates the importance of CYP2A6 in the regulation of tobacco consumption behaviors, procarcinogen exposure and metabolism in both light smokers and smokeless tobacco users.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.