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The value of biosamples in smoking cessation trials: a review of genetic, metabolomic, and epigenetic findings

Research output: Contribution to journalArticle

Original languageEnglish
Article numberntx096
Pages (from-to)403-413
Number of pages11
JournalNicotine and Tobacco Research
Volume20
Issue number4
Early online date3 May 2017
DOIs
DateAccepted/In press - 24 Apr 2017
DateE-pub ahead of print - 3 May 2017
DatePublished (current) - 6 Mar 2018

Abstract

Introduction: Human genetic research has succeeded in definitively identifying multiple genetic variants associated with risk for nicotine dependence and heavy smoking. To build on these advances, and to aid in reducing the prevalence of smoking and its consequent health harms, the next frontier is to identify genetic predictors of successful smoking cessation and also of the efficacy of smoking cessation treatments ("pharmacogenomics"). More broadly, additional biomarkers that can be quantified from biosamples also promise to aid "Precision Medicine" and the personalization of treatment, both pharmacological and behavioral. Aims and Methods: To motivate ongoing and future efforts, here we review several compelling genetic and biomarker findings related to smoking cessation and treatment. Results: These Key results involve genetic variants in the nicotinic receptor subunit gene CHRNA5, variants in the nicotine metabolism gene CYP2A6, and the nicotine metabolite ratio. We also summarize reports of epigenetic changes related to smoking behavior. Conclusions: The results to date demonstrate the value and utility of data generated from biosamples in clinical treatment trial settings. This article cross-references a companion paper in this issue that provides practical guidance on how to incorporate biosample collection into a planned clinical trial and discusses avenues for harmonizing data and fostering consortium-based, collaborative research on the pharmacogenomics of smoking cessation. Implications: Evidence is emerging that certain genotypes and biomarkers are associated with smoking cessation success and efficacy of smoking cessation treatments. We review key findings that open potential avenues for personalizing smoking cessation treatment according to an individual's genetic or metabolic profile. These results provide important incentive for smoking cessation researchers to collect biosamples and perform genotyping in research studies and clinical trials.

    Research areas

  • nicotine, nicotine dependence, smoking, metabolism, smoking cessation, biological markers, DNA methylation, genes, genotype, genetics, epigenetics, cyp2a6 gene, metabolites

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Oxford University Press at https://academic.oup.com/ntr/article-lookup/doi/10.1093/ntr/ntx096. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 712 KB, PDF-document

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