Project 2: Understanding Adolescent Trajectories, Exposures and Suscep

大多数吸烟者和无烟烟草（ST）使用者开始在18岁之前。在青少年中， ST的使用一直在增加，ST使用和吸烟的双重使用率很高，甚至更高 俄亥俄州比其他许多州都多。目前的市场环境可能会使这一增长。然而，在这方面， 关于青少年开始使用ST和双重使用以及其常规使用的轨迹几乎一无所知， 依赖;通过生物标志物暴露;环境和遗传风险因素。该项目AD- 服装3 FDA研究优先事项：1）“烟草中尼古丁和其他成瘾物质的含量与 随着无烟烟草使用者，包括咀嚼烟草使用者逐渐产生依赖性， 鼻烟，鼻烟，和可溶性烟草产品？“2）“什么新的生物和生理标志物（包括 遗传和表观遗传标记）是吸烟相关和无烟烟草相关不良反应的预测因子。 健康成果？“3）对香料和味道的敏感性的遗传变异如何影响烟草 上瘾？“为了做到这一点，我们将跟踪一群青少年， 定期使用和依赖，他们的尼古丁暴露程度与生化确认， 尼古丁依赖水平（n= 2，010，包括研究结束时预计的661名烟草使用者）。我们 将测量致癌物暴露，并与同期队列和家庭为基础的协会设计，我们将 考虑各种遗传风险因素。具体目的是：1）确定从实验到 定期使用/依赖烟草产品（吸烟、ST和双重用途，包括新产品和新兴产品）， 基于产品中的尼古丁水平并针对来自环境的起始的预测因子进行调整（例如， 家庭和同伴烟草使用、广告和媒体）。我们假设，定期使用和依赖的时间 对于双重使用者，比单独使用ST或吸烟者更低。2)为了确定暴露的差异， 每天或几乎每天使用ST的青少年、吸烟者和双重使用者的烟草毒物 常规和新型暴露生物标志物（如代谢组学）。我们假设暴露在双重 使用者比ST使用者或吸烟者高。3)为了确定影响ST使用的易感性遗传学， 吸烟和双重用途，即，尼古丁代谢率、尼古丁代谢基因、神经行为基因、 味觉我们假设，遗传易感性和基因-环境相互作用导致增加 烟草使用的开始和类型，包括双重用途。实地工作将由研究中心进行， 调查和保留核心，并使用相同的队列在同伴项目1中进行研究，提供 一个丰富的资源，为有关接触营销和看法的信息。为了提高普遍性， 在我们的研究成果中，我们将研究农村和城市的青少年男性及其家庭。我们将加强 使用共同措施的项目之间的协同作用。这项研究的信息将有助于FDA 决定在以下情况下对烟草产品的营销施加何种限制（如果有的话）： 青年启蒙和双重用途，烟草营销和促销的管制， 向易受双重用途影响的青少年宣传，制定与 烟草暴露和调味品，以及开发更好的测试来确定烟草相关的健康风险。

Most smokers and smokeless tobacco (ST) users begin before the age of 18. In adolescents, the prevalence of ST use has been increasing and the prevalence of dual use for ST use and smoking is high, and even higher in Ohio than many other states. The current marketing environment will likely make this increase. However, almost nothing is known about adolescent initiation of ST and dual use with their trajectories to regular use and dependence; exposures through biomarkers, and; environmental and genetic risk factors. This project ad- dresses 3 FDA research priorities: 1) "What level of nicotine and other addictive substances in tobacco is associated with progression to dependence among smokeless tobacco users, including users of chewing tobacco, snuff, snus, and dissolvable tobacco products?" 2) "What novel biological and physiological markers (including genetic and epigenetic markers) are predictive of smoking-related and smokeless tobacco-related adverse. health outcomes?" 3) How does genetic variation in sensitivity to flavorings and taste influence tobacco addiction?" To do this, we will follow a cohort of adolescents and establish their trajectories from experimentation to regular use and dependence, their degree of nicotine exposure with biochemical confirmation, and their level of nicotine dependence (n=2,010, including a projected 661 tobacco users at the end of the study). We will measure carcinogen exposures and with concurrent cohort and family based association designs, we will consider various genetic risk factors. The Specific Aims are: 1) To determine the time from experimentation to regular use/dependence for tobacco products (smoking, ST and dual use, including new and emerging products), based on nicotine levels in products and adjusted for predictors of initiation from the environment (e.g., family and peer tobacco use, advertising and media). We hypothesize that the time to regular use and dependence is less for dual users than for exclusive ST use or smoking. 2) To determine the differences in exposure to tobacco toxicants for daily or almost daily ST users, smokers, and dual users among adolescents using conventional and novel biomarkers of exposure (e.g. metabolomics). We hypothesize that exposures in dual users are higher than for ST users or smokers. 3) To identify genetics of susceptibility that influence ST use, smoking and dual use, i.e., the nicotine metabolic ratio and genes of nicotine metabolism, neurobehavior and taste perception. We hypothesize that genetic susceptibilities and gene-environment interactions leads to increased initiation and type of tobacco use, including dual use. The field work will be conducted by the Research, Survey and Retention Core, and using the same cohort to be studied in companion Project 1, providing a rich resource for information about exposure to marketing and perceptions. To enhance the generalizability of our research results, we will study both rural and urban adolescent males, and their families. We will enhance synergy among the projects that use shared measures. The information from this study will help FDA decision making about what restrictions, if any, to place on the marketing of tobacco products in the context of youth initiation and dual use, the regulation of tobacco marketing and promotion, the decision to target healthrelated communications to adolescents susceptible to dual use, development of product standards related to exposures and flavorings, and the development of better tests to identify tobacco-related health risks.