Project 2: Understanding Adolescent Trajectories, Exposures and Suscep

项目 2：了解青少年轨迹、暴露和 Suscep

• 批准号: 9333247
• 负责人: Peter G. Shields
• 金额: $ 55.13万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9333247
• 关键词: Address; Adolescent; Adopted; Adult; Advertising; Age; Appalachian Region; Area; Biochemical; Biological; Biological Markers; Carcinogen Screening; Carcinogen exposure; Chemicals; Cigarette; Communication; Companions; Data; Decision Making; Dependence; Development; Diabetes Mellitus; Emerging Technologies; Environment; Environmental Risk Factor; Exposure to; Family; Flavoring; Food Preferences; Genes; Genetic; Genetic Markers; Genetic Predisposition to Disease; Genetic Variation; Genetic study; Health; Health Communication; Heritability; Industry; Longitudinal Studies; Male Adolescents; Marketing; Measures; Menthol; Metabolic; Metabolism; Nested Case-Control Study; Nicotine; Nicotine Dependence; Nitrosamines; Obesity; Ohio; Oral Tobacco; Outcome; Perception; Physiological; Policies; Population; Predisposition; Prevalence; Primary Prevention; Reaction; Regulation; Research; Research Design; Research Priority; Resources; Risk; Rural; Smoke; Smokeless; Smokeless Tobacco; Smoker; Smoking; Surveys; Sweden; Taste Perception; Testing; Time; Tobacco; Tobacco Dependence; Tobacco smoking; Tobacco use; Toxicant exposure; Work; Youth; addiction; base; cohort; design; epigenetic marker; family influence; gene environment interaction; genetic risk factor; metabolomics; neurobehavior; novel; novel marker; peer; peer influence; prevent; product development; snuff; snus; specific biomarkers; synergism; tobacco advertising; tobacco regulatory science; toxicant; trait

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.

大多数吸烟者和无烟烟草(ST)使用者在18岁之前就开始吸烟。 ST的使用一直在增加，ST使用和吸烟的双重使用的流行率很高，甚至更高 在俄亥俄州比其他许多州都多。目前的营销环境可能会使这一数字增加。然而， 几乎对青少年开始使用ST和双重使用及其正常使用的轨迹和 依赖；通过生物标记物暴露；环境和遗传风险因素。这个项目的广告- Dresses 3 FDA的研究重点：1)烟草中尼古丁和其他成瘾物质的水平与 随着无烟烟草使用者，包括咀嚼烟草使用者的依赖程度的发展， 鼻烟、鼻烟和可溶性烟草产品？“2)”哪些新的生物和生理标记(包括 遗传和表观遗传标记)可以预测与吸烟相关和与无烟烟草相关的不良反应。 健康结果？3)对调味品和味道的敏感度遗传变异如何影响烟草 为了做到这一点，我们将跟踪一组青少年，并从实验中确定他们的轨迹 经常使用和依赖，他们接触尼古丁的程度和生化确认，以及他们的 尼古丁依赖程度(n=2,010，包括研究结束时预计的661名吸烟者)。我们 将测量致癌物暴露，并通过同时进行的队列和基于家庭的关联设计，我们将 考虑各种遗传风险因素。具体目标是：1)确定从实验到 经常使用/依赖烟草产品(吸烟、性侵犯和双重用途，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启动的预测因素进行调整(例如， 家庭和同龄人烟草使用、广告和媒体)。我们假设，时间要经常使用和依赖 对于双重用户来说，比单独使用ST或吸烟更少。2)确定暴露的差异 对每天或几乎每天吸食ST、吸烟者和青少年中双重吸毒者的烟草毒物 暴露的常规和新型生物标记物(例如代谢组学)。我们假设曝光量是双重的 用户高于ST用户或吸烟者。3)确定影响ST使用的易感性的遗传学， 吸烟和双重用途，即尼古丁代谢率和尼古丁代谢基因，神经行为和 味觉。我们假设遗传易感性和基因-环境相互作用导致 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配套项目1中进行研究，提供 一个丰富的资源，提供有关市场营销和认知方面的信息。增强可推广性 在我们的研究成果中，我们将研究农村和城市青少年男性及其家庭。我们将加强 使用共享措施的项目之间的协同作用。这项研究的信息将有助于FDA 关于在下列情况下对烟草产品的销售施加什么限制(如果有的话)的决定 青年启动和两用、烟草营销和推广的管理、以保健为目标的决定 向易受双重用途影响的青少年进行交流，制定与以下方面相关的产品标准 暴露和调味品，以及开发更好的测试来确定与烟草有关的健康风险。