Meghan J Chenoweth1, Marie-Pierre Sylvestre2, Gisele Contreras3, Maria Novalen4, Jennifer O'Loughlin5, Rachel F Tyndale6. 1. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Electronic address: meghan.chenoweth@utoronto.ca. 2. Axe Risques à la santé, CRCHUM, Montréal, QC, Canada; Department of Social and Preventive Medicine, School of Public Health, University of Montréal, Montréal, QC, Canada. Electronic address: marie-pierre.sylvestre@umontreal.ca. 3. Axe Risques à la santé, CRCHUM, Montréal, QC, Canada; Department of Social and Preventive Medicine, School of Public Health, University of Montréal, Montréal, QC, Canada. Electronic address: gisele.contreras@umontreal.ca. 4. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Electronic address: m.novalen@utoronto.ca. 5. Axe Risques à la santé, CRCHUM, Montréal, QC, Canada; Department of Social and Preventive Medicine, School of Public Health, University of Montréal, Montréal, QC, Canada. Electronic address: jennifer.oloughlin@umontreal.ca. 6. Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: r.tyndale@utoronto.ca.
Abstract
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 self-reported 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). CONCLUSIONS: Our findings extend previous work indicating that slow nicotine metabolism mediated by CYP2A6, and perhaps CYP2B6, increases risk for tobacco dependence throughout adolescence.
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 self-reported cigarette consumption and salivarycotinine. 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 salivarycotinine, a biomarker of tobacco exposure, acquired at age 24 (B=0.37; P<0.001). CONCLUSIONS: Our findings extend previous work indicating that slow nicotine metabolism mediated by CYP2A6, and perhaps CYP2B6, increases risk for tobacco dependence throughout adolescence.
Authors: Neal L Benowitz; Gary E Swan; Peyton Jacob; Christina N Lessov-Schlaggar; Rachel F Tyndale Journal: Clin Pharmacol Ther Date: 2006-11 Impact factor: 6.875
Authors: Anna M Lee; Christopher Jepson; Peter G Shields; Neal Benowitz; Caryn Lerman; Rachel F Tyndale Journal: Cancer Epidemiol Biomarkers Prev Date: 2007-06 Impact factor: 4.254
Authors: Janet Audrain-McGovern; Nael Al Koudsi; Daniel Rodriguez; E Paul Wileyto; Peter G Shields; Rachel F Tyndale Journal: Pediatrics Date: 2006-11-27 Impact factor: 7.124
Authors: M Rotger; H Tegude; S Colombo; M Cavassini; H Furrer; L Décosterd; J Blievernicht; T Saussele; H F Günthard; M Schwab; M Eichelbaum; A Telenti; U M Zanger Journal: Clin Pharmacol Ther Date: 2007-01-18 Impact factor: 6.875
Authors: Ulla Broms; Karri Silventoinen; Pamela A F Madden; Andrew C Heath; Jaakko Kaprio Journal: Twin Res Hum Genet Date: 2006-02 Impact factor: 1.587
Authors: Meghan J Chenoweth; Maria Novalen; Larry W Hawk; Robert A Schnoll; Tony P George; Paul M Cinciripini; Caryn Lerman; Rachel F Tyndale Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-07-10 Impact factor: 4.254
Authors: Stephen T Higgins; Michael DeSarno; Danielle R Davis; Tyler Nighbor; Joanna M Streck; Shana Adise; Roxanne Harfmann; Riley Nesheim-Case; Catherine Markesich; Derek Reed; Rachel F Tyndale; Diann E Gaalema; Sarah H Heil; Stacey C Sigmon; Jennifer W Tidey; Andrea C Villanti; Dustin Lee; John R Hughes; Janice Y Bunn Journal: Prev Med Date: 2020-07-03 Impact factor: 4.018
Authors: Emily Olfson; Joseph Bloom; Sarah Bertelsen; John P Budde; Naomi Breslau; Andrew Brooks; Robert Culverhouse; Grace Chan; Li-Shiun Chen; David Chorlian; Danielle M Dick; Howard J Edenberg; Sarah Hartz; Dorothy Hatsukami; Victor M Hesselbrock; Eric O Johnson; John R Kramer; Samuel Kuperman; Jacquelyn L Meyers; John Nurnberger; Bernice Porjesz; Nancy L Saccone; Marc A Schuckit; Jerry Stitzel; Jay A Tischfield; John P Rice; Alison Goate; Laura J Bierut Journal: Addict Biol Date: 2016-12-29 Impact factor: 4.280
Authors: Stephani L Stancil; Robin E Pearce; Rachel F Tyndale; Gregory L Kearns; Carrie A Vyhlidal; J Steven Leeder; Susan Abdel-Rahman Journal: Br J Clin Pharmacol Date: 2019-03-12 Impact factor: 4.335
Authors: Brian V Fix; Richard J O'Connor; Neal Benowitz; Bryan W Heckman; K Michael Cummings; Geoffrey T Fong; James F Thrasher Journal: Nicotine Tob Res Date: 2017-09-01 Impact factor: 4.244
Authors: Haidy K Giratallah; Meghan J Chenoweth; Newton Addo; Jasjit S Ahluwalia; Lisa Sanderson Cox; Caryn Lerman; Tony P George; Neal L Benowitz; Rachel F Tyndale Journal: Drug Alcohol Depend Date: 2021-04-20 Impact factor: 4.852
Authors: Yadira X Perez-Paramo; Gang Chen; Joseph H Ashmore; Christy J W Watson; Shamema Nasrin; Jennifer Adams-Haduch; Renwei Wang; Yu-Tang Gao; Woon-Puay Koh; Jian-Min Yuan; Philip Lazarus Journal: Cancer Epidemiol Biomarkers Prev Date: 2018-10-31 Impact factor: 4.254
Authors: Lion Shahab; Emily Mortimer; Linda Bauld; Jennifer A McGowan; Ann McNeill; Rachel F Tyndale Journal: Sci Rep Date: 2017-12-14 Impact factor: 4.379