Nicotine Metabolism and the Development of Addiction in Adolescent Light Smokers

描述(申请人提供)：研究表明，存在与尼古丁新陈代谢较慢相关的某些遗传标记的成年吸烟者吸烟较少，更有可能戒烟。尽管尼古丁代谢似乎可能会影响吸烟者对尼古丁的依赖程度，但对尼古丁依赖发展的影响并不那么明显。由于成瘾最常发生在青春期，所以对这一时期吸烟的前瞻性研究对于我们了解尼古丁代谢在成瘾过程中的作用是至关重要的。目的：探讨尼古丁代谢率是否影响青少年对尼古丁成瘾的易感性。具体目标：我们将在青少年早期/实验吸烟者的预期队列中研究尼古丁代谢率和随时间推移的香烟消费之间的关系(目标1)。我们还将研究青少年早期/实验性吸烟者尼古丁代谢率与成瘾发展之间的关系(目标2)。研究设计：采用前瞻性队列设计，我们将检验尼古丁代谢率(通过3‘-羟基可替宁/可替宁比率衡量)对青少年早期/实验吸烟者(13-16岁，每周吸烟1-14支)尼古丁成瘾发展的影响。在基线时，将进行吸烟行为和成瘾问卷调查，并采集唾液样本以确定尼古丁代谢率。然后，所有受试者将每隔6个月至36个月接受一次检查。上瘾将通过增加唾液中的可替宁水平来衡量，反映摄入量的增加以及尼古丁成瘾迹象和症状的发展，使用标准化的量表。意义：这项拟议的研究对于理解一些青少年吸烟者为什么以及如何从试验性吸烟者转变为上瘾吸烟者至关重要。虽然只有一小部分青少年吸烟，但我们知道，那些成年后继续吸烟的人吸烟严重的可能性更大，戒烟的可能性更小，考虑到吸烟相关毒素的累积影响，因吸烟而产生负面后果的风险增加。因此，对青少年吸烟者进行早期干预对于遏制吸烟的破坏性影响至关重要。此外，由于对成年吸烟者的研究表明，对戒烟药物治疗的反应可能会受到吸烟者个人尼古丁代谢率的影响，在为青少年选择特定形式的尼古丁替代品时，代谢率可能被证明同样有用。因此，研究尼古丁代谢对青少年吸烟者的影响可能会提供新的重要见解，了解哪些青少年可以从尼古丁替代中受益，哪些更有可能从非尼古丁药物治疗或非药物干预中受益。公共卫生相关性：这项研究的数据将为我们提供有关一些青少年吸烟者为什么以及如何从实验吸烟者转变为上瘾吸烟者的基本信息。随着我们更好地了解青少年尼古丁成瘾，我们可以改进青少年吸烟者的预防和治疗策略，从而预防与烟草使用有关的多种可预防的癌症。

DESCRIPTION (provided by applicant): Studies have shown that adult smokers with the presence of certain genetic markers associated with slower nicotine metabolism smoke fewer cigarettes and are more likely to quit. Although it seems likely that nicotine metabolism affects the degree of nicotine dependence in smokers, the impact on the development of nicotine dependence is less clear. Since addiction most frequently occurs during adolescence, prospective studies that focus on smoking during this time period are essential to give us information on the effects of nicotine metabolism on the progression to addiction. Objective: To ascertain whether the rate of nicotine metabolism affects adolescents' susceptibility to nicotine addiction. Specific aims: We will examine the association between the rate of nicotine metabolism and cigarette consumption over time in a prospective cohort of adolescent early/experimental smokers (Aim 1). We will also examine the association between the rate of nicotine metabolism and the development of addiction in adolescent early/experimental smokers (Aim 2). Study design: Using a prospective cohort design, we will examine the influence of the rate of nicotine metabolism (measured by the 3'-hydroxycotinine/cotinine ratio) on the development of nicotine addiction in adolescent early/experimental smokers (13-16 years-old who smoke 1-14 cigarettes per week). At baseline, smoking behavior and addiction questionnaires will be administered and saliva samples will be obtained for determination of nicotine metabolic rate. All subjects will then be seen at 6 month intervals up to 36 months. Addiction will be measured by increasing salivary cotinine levels reflecting increased intake and the development of nicotine addiction signs and symptoms using standardized scales. Significance: The proposed research is critical to understanding why and how some adolescent smokers make the transition from experimentation to addicted smoker. Although only a small percentage of teens smoke cigarettes, we know that those who continue smoking into adulthood are more likely to smoke heavily, less likely to quit and given the cumulative effect of smoking related toxins, are at increased risk for developing negative outcomes from smoking. Therefore, intervening early among adolescent smokers is essential to halt the devastating effects from smoking. Moreover, as studies of adult smokers have suggested that response to pharmacotherapy for smoking cessation may be influenced by a smoker's individual rate of nicotine metabolism, the metabolic rate may prove equally useful when choosing specific forms of nicotine replacement for adolescents. Therefore, research into the effect of nicotine metabolism on adolescent smokers may provide new and important insights into which teens may benefit from nicotine replacement and which may be more likely to benefit from non-nicotine pharmacotherapy or non- pharmacologic interventions. PUBLIC HEALTH RELEVANCE: Data derived from this study will provide us with essential information about why and how some adolescent smokers make the transition from experimentation to addicted smoker. As we better understand adolescent nicotine addiction, we can improve prevention and treatment strategies for adolescent smokers and thus prevent the multitude of preventable cancers associated with tobacco use.