Dataset Information

The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race, and sex.

ABSTRACT: Cotinine, 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.Cotinine 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).Study 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.In people with slower relative to faster CYP2A6 activity, cotinine accumulates resulting in substantial differences in cotinine levels for a given tobacco exposure.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.

SUBMITTER: Zhu AZ

PROVIDER: S-EPMC3617060 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race, and sex.

Zhu Andy Z X AZ Renner Caroline C CC Hatsukami Dorothy K DK Swan Gary E GE Lerman Caryn C Benowitz Neal L NL Tyndale Rachel F RF

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20130131 4

<h4>Background</h4>Cotinine, 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.<h4>Methods</h4>Cotinine 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 ( ...[more]

PMID: 23371292

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Project description:Background and aimsDue to concerns about increased exposure to nicotine, pregnant women using nicotine replacement therapy (NRT) to stop smoking are usually advised to stop using NRT if they relapse to smoking. This study investigated whether this is justified. We compared changes in saliva cotinine from baseline to 2 weeks post-target quit date pregnant smokers who relapsed to smoking and continued to use their patches having been assigned to use nicotine patches or placebo.Design and settingControlled pre-post design stratified by intervention condition from the 'Study of Nicotine Patch in Pregnancy', a randomized, placebo-controlled trial.ParticipantsA sample of 268 pregnant women, assigned placebo (n = 122) or nicotine (n = 146) patches, who returned for further supplies of patches and who reported any smoking in the week prior to a visit at 2 weeks after their target quit date.MeasurementsSaliva cotinine concentrations were measured at baseline and 2 weeks after participants' target quit dates. Any smoking in the previous week was assessed by self-report, validated by expired air carbon monoxide (CO).FindingsThere was no change in saliva cotinine concentrations between baseline and 2 weeks post-target quit date in saliva cotinine concentration in the nicotine patch group [ratio of geometric means = 0.94, 95% confidence interval (CI) = 0.83 to 1.07; P = 0.37, Bayes factor = 0.15]. However, there was a reduction in reported number of cigarettes smoked/day (mean difference -6, 95% CIs -7 to -5, P < 0.001) and in CO concentrations (mean difference -3.0 parts per million, 95% CIs -4.2 to -1.9, P < 0.001). These changes were not significantly different from changes in the placebo group except for cigarette consumption, which reduced more in the nicotine group (P = 0.046).ConclusionsIn women trying to stop smoking with the aid of a nicotine patch but having smoked at 2 weeks post-target quit, their nicotine concentration did not change from baseline, but they reported smoking fewer cigarettes and had lower carbon monoxide concentrations.

Dataset Information

The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race, and sex.

Publications

The ability of plasma cotinine to predict nicotine and carcinogen exposure is altered by differences in CYP2A6: the influence of genetics, race, and sex.

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