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 岁之前开始吸烟。在青少年中， 无烟烟草的使用一直在增加，无烟烟草和吸烟双重使用的流行率很高，甚至更高 俄亥俄州比许多其他州都多。当前的营销环境可能会促使这一增长。然而， 关于青少年开始使用 ST 和双重使用及其到定期使用和使用的轨迹几乎一无所知 依赖；通过生物标志物进行暴露；环境和遗传风险因素。该项目广告 FDA 的 3 个研究重点：1）“烟草中尼古丁和其他成瘾物质的含量与什么水平相关？” 随着无烟烟草使用者（包括咀嚼烟草使用者）逐渐形成依赖， 鼻烟、鼻烟和可溶解烟草制品？” 2) “有哪些新颖的生物和生理标记（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性的遗传变异如何影响烟草 成瘾？”为此，我们将跟踪一群青少年并通过实验确定他们的轨迹 经常使用和依赖，通过生化确认的尼古丁暴露程度，以及他们的尼古丁暴露程度 尼古丁依赖程度（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，并通过同时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/依赖烟草制品（吸烟、无烟烟草和双重用途，包括新产品和新兴产品）， 基于产品中的尼古丁含量，并根据环境中起始的预测因素进行调整（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 对于双重用户来说，比单独使用 ST 或吸烟时要少。 2) 确定曝光差异 每天或几乎每天使用 ST 的人、吸烟者和青少年中双重使用者的烟草毒物 传统和新颖的暴露生物标志物（例如代谢组学）。我们假设双重暴露 使用者的比例高于 ST 使用者或吸烟者。 3) 确定影响 ST 使用的易感性遗传学， 吸烟和双重使用，即尼古丁代谢比率和尼古丁代谢基因、神经行为和 味觉感知。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，包括双重使用。实地工作将由研究机构进行， 调查和保留核心，并使用同一队列在配套项目 1 中进行研究，提供 有关营销和认知的信息的丰富资源。增强普遍性 根据我们的研究成果，我们将研究农村和城市的男性青少年及其家庭。我们将加强 使用共享措施的项目之间的协同作用。这项研究的信息将帮助 FDA 就在以下情况下对烟草制品的营销施加哪些限制（如果有）做出决定 青少年启动和双重使用、烟草营销和促销的监管、以健康相关为目标的决定 与易受双重用途影响的青少年进行沟通，制定相关产品标准 接触和调味品，以及开发更好的测试来识别与烟草相关的健康风险。