Exploring Potential for a Personalized Medicine Approach to Smoking Cessation With an American Indian Tribe

Abstract Introduction A potential precision medicine approach to smoking cessation is tailoring pharmacotherapy to a biomarker known as the nicotine metabolite ratio (NMR). Little is known about the potential impact and acceptability of this approach for American Indian (AI) persons. Aims and Methods Tribal-academic collaboration was formed and during 2019–2020 AI adults who smoke(N = 54) were recruited to (1) examine correlations between NMR, dependence, and smoking exposure; (2) assess the extent to which pharmacotherapy preference aligned with NMR-informed recommendations; (3) explore acceptability of NMR-informed pharmacotherapy selection. Participants provided samples for assessment of salivary NMR and urinary total nicotine equivalents (TNE) and completed a questionnaire that assessed cigarettes per day (CPD), Fagerstrom Test for Cigarette Dependence (FTCD), pharmacotherapy preference, and perceptions of NMR-informed pharmacotherapy selection. Results Significant positive correlations were observed between NMR and FTCD (r = 0.29;p = .0383) and its abbreviated version Heaviness of Smoking Index (HIS) (r = 0.28;p =.0426). Post-hoc analyses suggest that relationships between dependence and NMR were driven by time to first cigarette. Nonsignificant, but directionally consistent, relationships were observed between NMR and CPD (r = 0.21; p =0.1436) and TNE (r = 0.24;p = .2906). Most participants preferred nicotine replacement therapy (71%) over varenicline (29%) and preference for pharmacotherapy matched NMR-based recommendations in 54% of participants. NMR-informed pharmacotherapy selection was supported by 62% of participants. Conclusion In a sample of AI adults who smoke, NMR was related to cigarette dependence and about one-half of participants’ pharmacotherapy preference matched their NMR-informed recommendation. There was lower acceptability of NMR-informed approach in this sample of AI adults than prior studies among white or black/African American people who smoke. Implications Relationships between NMR, dependence, and self-preference for pharmacotherapy suggest that NMR-informed pharmacotherapy selection may have potential for enhancing smoking quitting success in this Tribe. Lower acceptability of NMR-informed pharmacotherapy in this Tribe suggests that this approach may not be equitably utilized. Future work could include identifying community-driven solutions to mitigate precision medicine concerns.

[1]  Ashley B Cole,et al.  Racial/ethnic group comparisons of quit ratios and prevalences of cessation-related factors among adults who smoke with a quit attempt , 2021, The American journal of drug and alcohol abuse.

[2]  J. Prochaska,et al.  Correlates of the nicotine metabolite ratio in Alaska Native people who smoke cigarettes. , 2021, Experimental and clinical psychopharmacology.

[3]  A. Begnaud,et al.  Recommendations to researchers for aiding in increasing American Indian representation in genetic research and personalized medicine , 2020, Personalized medicine.

[4]  Elizabeth A. Scoville,et al.  Precision nicotine metabolism-informed care for smoking cessation in Crohn’s disease: A pilot study , 2020, PloS one.

[5]  P. Spicer,et al.  An Alaska Native community’s views on genetic research, testing, and return of results: Results from a public deliberation , 2020, PloS one.

[6]  C. Lerman,et al.  The Use of the Nicotine Metabolite Ratio as a Biomarker to Personalize Smoking Cessation Treatment: Current Evidence and Future Directions , 2020, Cancer Prevention Research.

[7]  F. J. McClernon,et al.  Relationships between the Nicotine Metabolite Ratio and a Panel of Exposure and Effect Biomarkers: Findings from Two Studies of U.S. Commercial Cigarette Smokers , 2020, Cancer Epidemiology, Biomarkers & Prevention.

[8]  Nicole Senft,et al.  Attitudes toward Precision Treatment of Smoking in the Southern Community Cohort Study , 2019, Cancer Epidemiology, Biomarkers & Prevention.

[9]  D. Thompson,et al.  The relationship between nicotine metabolism and nicotine and carcinogen exposure among American Indian commercial cigarette smokers and electronic nicotine delivery system users. , 2019, Addictive behaviors.

[10]  Elizabeth A. Scoville,et al.  Nicotine Metabolism-informed Care for Smoking Cessation: A Pilot Precision RCT , 2018, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[11]  B. Howard,et al.  Variation in CYP2A6 and nicotine metabolism among two American Indian tribal groups differing in smoking patterns and risk for tobacco-related cancer , 2017, Pharmacogenetics and genomics.

[12]  L. Hawk,et al.  Racial differences in the relationship between rate of nicotine metabolism and nicotine intake from cigarette smoking , 2016, Pharmacology Biochemistry and Behavior.

[13]  D. Erickson,et al.  Cigarette Smoking Among Urban American Indian Adults - Hennepin and Ramsey Counties, Minnesota, 2011. , 2016, MMWR. Morbidity and mortality weekly report.

[14]  L. Le Marchand,et al.  Genetic determinants of CYP2A6 activity across racial/ethnic groups with different risks of lung cancer and effect on their smoking intensity. , 2016, Carcinogenesis.

[15]  C. Lerman,et al.  Precision Medicine for Tobacco Dependence: Development and Validation of the Nicotine Metabolite Ratio , 2016, Journal of Neuroimmune Pharmacology.

[16]  L. Hawk,et al.  Use of the nicotine metabolite ratio as a genetically informed biomarker of response to nicotine patch or varenicline for smoking cessation: a randomised, double-blind placebo-controlled trial. , 2015, The Lancet. Respiratory medicine.

[17]  B. Lushniak,et al.  The Health consequences of smoking—50 years of progress : a report of the Surgeon General , 2014 .

[18]  L. Hawk,et al.  The relationship between the nicotine metabolite ratio and three self-report measures of nicotine dependence across sex and race , 2014, Psychopharmacology.

[19]  A. Mainous,et al.  Racial Differences in Attitudes toward Personalized Medicine , 2013, Public Health Genomics.

[20]  N. Benowitz,et al.  High dose transdermal nicotine for fast metabolizers of nicotine: a proof of concept placebo-controlled trial. , 2013, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[21]  D. Hatsukami,et al.  Alaska Native smokers and smokeless tobacco users with slower CYP2A6 activity have lower tobacco consumption, lower tobacco-specific nitrosamine exposure and lower tobacco-specific nitrosamine bioactivation. , 2013, Carcinogenesis.

[22]  Beth A. Glenn,et al.  Barriers to genetic testing for breast cancer risk among ethnic minority women: an exploratory study. , 2012, Ethnicity & disease.

[23]  D. Heitjan,et al.  Reproducibility of the Nicotine Metabolite Ratio in Cigarette Smokers , 2012, Cancer Epidemiology, Biomarkers & Prevention.

[24]  K. Fagerström Determinants of tobacco use and renaming the FTND to the Fagerstrom Test for Cigarette Dependence. , 2012, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[25]  M. Spitz,et al.  Relationship between CYP2A6 and CHRNA5-CHRNA3-CHRNB4 variation and smoking behaviors and lung cancer risk. , 2011, Journal of the National Cancer Institute.

[26]  H. McRobbie,et al.  Systematic review of the relationship between the 3-hydroxycotinine/cotinine ratio and cigarette dependence , 2011, Psychopharmacology.

[27]  Robyn L Sterling Genetic research among the Havasupai--a cautionary tale. , 2011, The virtual mentor : VM.

[28]  C. Lerman,et al.  Nicotine Metabolite Ratio Predicts Smoking Topography and Carcinogen Biomarker Level , 2011, Cancer Epidemiology, Biomarkers & Prevention.

[29]  C. Jepson,et al.  Genetic Variation in Nicotine Metabolism Predicts the Efficacy of Extended‐Duration Transdermal Nicotine Therapy , 2010, Clinical pharmacology and therapeutics.

[30]  N. Benowitz,et al.  Association of Nicotine Metabolite Ratio and CYP2A6 Genotype With Smoking Cessation Treatment in African‐American Light Smokers , 2009, Clinical pharmacology and therapeutics.

[31]  C. Lerman,et al.  Nicotine metabolic rate predicts successful smoking cessation with transdermal nicotine: A validation study , 2009, Pharmacology Biochemistry and Behavior.

[32]  L. Epstein,et al.  Toward Personalized Therapy for Smoking Cessation: A Randomized Placebo‐controlled Trial of Bupropion , 2008, Clinical pharmacology and therapeutics.

[33]  P. Villalta,et al.  Analysis of [3',3'-d(2)]-nicotine and [3',3'-d(2)]-cotinine by capillary liquid chromatography-electrospray tandem mass spectrometry. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[34]  N. Benowitz,et al.  Determinants of the rate of nicotine metabolism and effects on smoking behavior , 2006, Clinical pharmacology and therapeutics.

[35]  C. Lerman,et al.  Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation , 2006, Clinical pharmacology and therapeutics.

[36]  N. Benowitz,et al.  Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity , 2004, Clinical pharmacology and therapeutics.

[37]  C. Pomerleau,et al.  Nicotine metabolite ratio as a predictor of cigarette consumption. , 2003, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco.

[38]  R. Tyndale,et al.  Nicotine metabolism defect reduces smoking , 1998, Nature.

[39]  L. Kozlowski,et al.  The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. , 1991, British journal of addiction.

[40]  R C Frecker,et al.  Measuring the heaviness of smoking: using self-reported time to the first cigarette of the day and number of cigarettes smoked per day. , 1989, British journal of addiction.