<i>CYP2A6</i>Longitudinal Effects in Young Smokers

Cannon, Dale S.; Medina, Tait R.; Mermelstein, Robin J.; Hedeker, Donald; Bakian, Amanda V.; Coon, Hilary; Cook, Edwin H.; Hamil, Cindy; Weiss, Robert B.

doi:10.1093/ntr/ntv049

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…Differences between our findings and those from the longitudinal investigation (Cannon et al, 2015) may stem from differences in study design (cross-sectional vs. longitudinal), variation in assessment of CYP2A6 activity (categorical grouping of metabolism vs. use of a metabolism metric), and/or differences in smoking phenotypes examined (ICD-10 dependence status vs. NDSS score). Our small sample size for slow metabolizers (n=9) may have also affected statistical power.…”

Section: Discussioncontrasting

confidence: 73%

“…At age 16, CYP2A6 intermediate metabolism (vs. normal and slow metabolism) was associated with the highest nicotine dependence syndrome scale (NDSS) score; in contrast, as young adults (age 22), CYP2A6 normal metabolizers had the highest NDSS score (Cannon et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study of young smokers, the influence of CYP2A6 variation on smoking outcomes varied throughout the 6-year follow-up period (Cannon et al, 2015). At age 16, CYP2A6 intermediate metabolism (vs. normal and slow metabolism) was associated with the highest nicotine dependence syndrome scale (NDSS) score; in contrast, as young adults (age 22), CYP2A6 normal metabolizers had the highest NDSS score (Cannon et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

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Variation in CYP2A6 and tobacco dependence throughout adolescence and in young adult smokers

Chenoweth

Sylvestre

Contreras

et al. 2016

Drug and Alcohol Dependence

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Background-Smoking is influenced by genetic factors including variation in CYP2A6 and CYP2B6, which encode nicotine-metabolizing enzymes. In early adolescence, CYP2A6 slow nicotine metabolism was associated with higher dependence acquisition, but reduced cigarette consumption. Here we extend this work by examining associations of CYP2A6 and CYP2B6 with tobacco dependence acquisition in a larger sample of smokers followed throughout adolescence.Methods-White participants from the Nicotine Dependence in Teens cohort that had ever inhaled (n=421) were followed frequently from age 12-18 years. Cox's proportional hazards models compared the risk of ICD-10 tobacco dependence acquisition (score 3+) for CYP2A6 and CYP2B6 metabolism groups. Early smoking experiences, as well as amount smoked at end of follow-up, was also computed. At age 24 (N=162), we assessed concordance between selfreported cigarette consumption and salivary cotinine.Results-In those who initiated inhalation during follow-up, CYP2A6 slow (vs. normal) metabolizers were at greater risk of dependence (hazards ratio (HR)=2.3; 95% CI=1.1, 4.8); CYP2B6 slow (vs. normal) metabolizers had non-significantly greater risk (HR=1.5; 95% CI=0.8, 2.6). Variation in CYP2A6 or CYP2B6 was not significantly associated with early smoking symptoms or cigarette consumption at end of follow-up. At age 24, neither gene was significantly associated with dependence status. Self-reported consumption was associated with salivary cotinine, a biomarker of tobacco exposure, acquired at age 24 (B=0.37; P<0.001). CIHR Author Manuscript CIHR Author Manuscript CIHR Author ManuscriptConclusions-Our findings extend previous work indicating that slow nicotine metabolism mediated by CYP2A6, and perhaps CYP2B6, increases risk for tobacco dependence throughout adolescence.

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Section: Discussioncontrasting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Variation in CYP2A6 and tobacco dependence throughout adolescence and in young adult smokers

Chenoweth

Sylvestre

Contreras

et al. 2016

Drug and Alcohol Dependence

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“…Other studies suggest that the increased risk of slower metabolizers for developing nicotine dependence in adolescence disappears by young adulthood (Chenoweth et al, 2016). Cannon et al (2016) followed 296 participants across ages 16-24 years and found that using a CYP2A6 diplotype predictive metric, intermediate metabolism compared with slow and normal was a risk factor for smoking frequency and nicotine dependence. By the end of the study at age 24 years, however, the individuals with predicted normal metabolism were at greatest risk for these smoking behaviors.…”

Section: Discussionmentioning

confidence: 99%

“…Studies in youth present conflicting results regarding the effect of nicotine metabolism on the development of nicotine dependence and other smoking behaviors (Audrain-McGovern et al, 2007; Cannon et al, 2016; Chenoweth et al, 2016; Huang et al, 2005; Moolchan et al, 2009; O'Loughlin et al, 2004; Rubinstein et al, 2008; Rubinstein et al, 2013). Some studies suggest that slow nicotine metabolism is associated with an increased risk of nicotine dependence (Chenoweth et al, 2016; O'Loughlin et al, 2004; Rubinstein et al, 2013), possibly reflecting an increased sensitivity to initial nicotine exposure among youth who metabolize nicotine more slowly.…”

Section: Introductionmentioning

confidence: 99%

CYP2A6 metabolism in the development of smoking behaviors in young adults

et al. 2016

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Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Previous studies support that slow metabolizers smoke fewer cigarettes once nicotine dependent but provide conflicting results on the role of CYP2A6 in the development of dependence. By focusing on the critical period of young adulthood, this study examines the relationship of CYP2A6 variation and smoking milestones. A total of 1209 European American young adults enrolled in the Collaborative Study on the Genetics of Alcoholism were genotyped for CYP2A6 variants to calculate a previously well-validated metric that estimates nicotine metabolism. This metric was not associated with the transition from never smoking to smoking initiation nor with the transition from initiation to daily smoking (P > 0.4). But among young adults who had become daily smokers (n = 506), decreased metabolism was associated with increased risk of nicotine dependence (P = 0.03) (defined as Fagerström Test for Nicotine Dependence score ≥4). This finding was replicated in the Collaborative Genetic Study of Nicotine Dependence with 335 young adult daily smokers (P = 0.02). Secondary meta-analysis indicated that slow metabolizers had a 53 percent increased odds (OR = 1.53, 95 percent CI 1.11-2.11, P = 0.009) of developing nicotine dependence compared with normal metabolizers. Furthermore, secondary analyses examining four-level response of time to first cigarette after waking (>60, 31-60, 6-30, ≤5 minutes) demonstrated a robust effect of the metabolism metric in Collaborative Study on the Genetics of Alcoholism (P = 0.03) and Collaborative Genetic Study of Nicotine Dependence (P = 0.004), illustrating the important role of this measure of dependence. These findings highlight the complex role of CYP2A6 variation across different developmental stages of smoking behaviors.

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Genetic influences impacting nicotine use and abuse during adolescence: Insights from human and rodent studies

Goldberg

Gould

2022

Brain Research Bulletin

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CYP2A6Longitudinal Effects in Young Smokers

Cited by 7 publications

References 26 publications

Variation in CYP2A6 and tobacco dependence throughout adolescence and in young adult smokers

Variation in CYP2A6 and tobacco dependence throughout adolescence and in young adult smokers

CYP2A6 metabolism in the development of smoking behaviors in young adults

Genetic influences impacting nicotine use and abuse during adolescence: Insights from human and rodent studies

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