ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2013
The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race, and sex.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 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.
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Who cites it
64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 85 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
- Sex dependent genetic architecture of biochemically verified tobacco use.Psychiatry research · 2025Trial
- Racial disparities in intensity of smoke exposure and nicotine intake among low-dependence smokers.Drug and alcohol dependence · 2021Trial
- Evaluation of nicotine patch adherence measurement using self-report and saliva cotinine among abstainers in a smoking cessation trial.Drug and alcohol dependence · 2020Trial
- Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking.Pharmacology, biochemistry, and behavior · 2016Trial
- Cessation of alcohol consumption decreases rate of nicotine metabolism in male alcohol-dependent smokers.Drug and alcohol dependence · 2016Trial
- Does Extended Pre Quit Bupropion Aid in Extinguishing Smoking Behavior?Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2015Trial
- Nicotine Dependence, Nicotine Metabolism, and the Extent of Compensation in Response to Reduced Nicotine Content Cigarettes.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2015Trial
- Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups.Carcinogenesis · 2014Trial
- Faster CYP2A6 increases COPD and lung cancer risk by increasing smoking quantity: a mediated mendelian randomization and observational mediation study.Respiratory research · 2026Observational
- Article
- Exploring the roles of cytochrome P450 enzymes and their inhibitors in cancers and non-neoplastic human diseases.Archives of pharmacal research · 2025Review
- Mechanisms of altered hepatic drug disposition during pregnancy: small molecules.Expert opinion on drug metabolism & toxicology · 2025Review
- Article
- Simultaneous Measurement and Distribution Analysis of Urinary Nicotine, Cotinine, Trans-3'-Hydroxycotinine, Nornicotine, Anabasine, and Total Nicotine Equivalents in a Large Korean Population.Molecules (Basel, Switzerland) · 2023Article
- Urinary nicotine metabolites are associated with cognitive impairment among the elderly in southern China.Tobacco induced diseases · 2023Article
- Relating individual differences in the reinforcing value of smoking and dependence severity to nicotine exposure levels in vulnerable populations.Preventive medicine · 2022Article
- Hand nicotine as an independent marker of thirdhand smoke pollution in children's environments.The Science of the total environment · 2022Article
- Effect of menthol on nicotine reduction: Pooled results from two double-blind randomized controlled trials.Brain research bulletin · 2022Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundCotinine, a nicotine metabolite, is a biomarker of tobacco, nicotine, and carcinogen exposure. However, a given cotinine level may not represent the same tobacco exposure; for example, African-Americans have higher cotinine levels than Caucasians after controlling for exposure.
methodsCotinine levels are determined by the amount of cotinine formation and the rate of cotinine removal, which are both mediated by the enzyme CYP2A6. Because CYP2A6 activity differs by sex (estrogen induces CYP2A6) and genotype, their effect on cotinine formation and removal was measured in nonsmoking Caucasians (Study 1, n = 181) infused with labeled nicotine and cotinine. The findings were then extended to ad libitum smokers (Study 2, n = 163).
resultsStudy 1: Reduced CYP2A6 activity altered cotinine formation less than cotinine removal resulting in ratios of formation to removal of 1.31 and 1.12 in CYP2A6 reduced and normal metabolizers (P = 0.01), or 1.39 and 1.12 in males and females (P = 0.001), suggesting an overestimation of tobacco exposure in slower metabolizers. Study 2: Cotinine again overestimated tobacco and carcinogen exposure by 25% or more in CYP2A6 reduced metabolizers (≈2-fold between some genotypes) and in males.
conclusionsIn people with slower relative to faster CYP2A6 activity, cotinine accumulates resulting in substantial differences in cotinine levels for a given tobacco exposure. IMPACT: Cotinine levels may be misleading when comparing those with differing CYP2A6 genotypes within a race, between races with differing frequencies of CYP2A6 gene variants (i.e., African-Americans have higher frequencies of reduced function variants contributing to their higher cotinine levels), or between the sexes.
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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.