ArticlePharmacogenetics and genomics2017
Variation in CYP2A6 and nicotine metabolism among two American Indian tribal groups differing in smoking patterns and risk for tobacco-related cancer.
Article in Pharmacogenetics and genomics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- A Systematic Review Exploring Empirical Pharmacogenomics Research Within Global Indigenous Populations.Molecular genetics & genomic medicine · 2024Pooled it
- Nicotine metabolite ratio and clinically significant depressive symptoms in U.S. adults: A smoker-specific association.Medicine · 2026Observational
- Perspectives on Using Pharmacogenomics to Guide Tobacco Cessation: Survey Results From an American Indian Community.Clinical and translational science · 2025Article
- Effect of very low nicotine content cigarettes on smoking behavior in Chinese smokers with genotype-stratified nicotine metabolism rates.Frontiers in psychiatry · 2025Article
- Implementing community-engaged pharmacogenomics in Indigenous communities.Nature communications · 2024Article
- The use of biomarkers to guide precision treatment for tobacco use.Addiction neuroscience · 2023Article
- 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
- Building Environmental Health and Genomics Literacy among Healthcare Providers Serving Vulnerable Communities: An Innovative Educational Framework.International journal of environmental research and public health · 2022Article
- Genetics of substance use disorders in the era of big data.Nature reviews. Genetics · 2021Review
- Nicotine metabolism and its association with CYP2A6 genotype among Indigenous people in Alaska who smoke.Clinical and translational science · 2021Article
- Genetics of Smoking Behaviors in American Indians.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Article
- 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
- Evidence That Established Lung Cancer Mortality Disparities in American Indians Are Not Due to Lung Cancer Genetic Testing and Targeted Therapy Disparities.Clinical lung cancer · 2020Article
- Nicotine Addiction: Neurobiology and Mechanism.Journal of pharmacopuncture · 2020Review
- The Use of the Nicotine Metabolite Ratio as a Biomarker to Personalize Smoking Cessation Treatment: Current Evidence and Future Directions.Cancer prevention research (Philadelphia, Pa.) · 2020Review
- Determination of Urinary Caffeine Metabolites as Biomarkers for Drug Metabolic Enzyme Activities.Nutrients · 2019Article
- Genetic Polymorphism ofOpen access Macedonian journal of medical sciences · 2018Article
- Biomarkers of Exposure in ENDS Users, Smokers, and Dual Users of American Indian Descent.Tobacco regulatory science · 2018Article
- P450 Pharmacogenetics in Indigenous North American Populations.Journal of personalized medicine · 2018Review
- Variation in CYP2A6 Activity and Personalized Medicine.Journal of personalized medicine · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveThe Northern Plains (NP) and Southwest (SW) American Indian populations differ in their smoking patterns and lung cancer incidence. We aimed to compare CYP2A6 genetic variation and CYP2A6 enzyme activity (representative of the rate of nicotine metabolism) between the two tribal populations as these have previously been associated with differences in smoking, quitting, and lung cancer risk. PARTICIPANTS AND
methodsAmerican Indians (N=636) were recruited from two different tribal populations (NP in South Dakota, SW in Arizona) as part of a study carried out as part of the Collaborative to Improve Native Cancer Outcomes P50 Project. A questionnaire assessed smoking-related traits and demographics. Participants were genotyped for CYP2A6 genetic variants *1B, *2, *4, *7, *9, *12, *17, and *35. Plasma and/or saliva samples were used to measure nicotine's metabolites cotinine and 3'-hydroxycotinine and determine CYP2A6 activity (3'-hydroxycotinine/cotinine, i.e. the nicotine metabolite ratio, NMR).
resultsThe overall frequency of genetically reduced nicotine metabolizers, those with CYP2A6 decrease-of-function or loss-of-function alleles, was lower in the NP compared with the SW (P=0.0006). The CYP2A6 genotype was associated with NMR in both tribal groups (NP, P<0.0001; SW, P=0.04). Notably, the rate of nicotine metabolism was higher in NP compared with SW smokers (P=0.03), and in comparison with other ethnic groups in the USA. Of the variables studied, the CYP2A6 genotype was the only variable to significantly independently influence NMR among smokers in both tribal populations (NP, P<0.001; SW, P=0.05).
conclusionUnique CYP2A6 allelic patterns and rates of nicotine metabolism among these American Indian populations suggest different risks for smoking, and tobacco-related disease.
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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.