Alcohol metabolism and disease risk in Asians: Examining the impact of personalized phenotypic/genotypic feedback and motivational processes on early drinking trajectories

亚洲人的酒精代谢和疾病风险：检查个性化表型/基因型反馈和动机过程对早期饮酒轨迹的影响

• 批准号: 10404917
• 负责人: SUSAN E LUCZAK
• 金额: $ 15.47万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10404917
• 关键词: Acculturation; Acetaldehyde; Acetates; Address; Affect; Alcohol consumption; Alcohol dehydrogenase; Alcoholic beverage heavy drinker; Alcohols; Alleles; Antacids; Antihistamines; Asian; Asian ancestry; Asian population; Behavioral Mechanisms; Benefits and Risks; Cancer Etiology; Carcinogens; Communication; Communities; Control Groups; DNA; Data; Diagnosis; Disease; East Asian; Environment; Enzymes; Esophagus; Ethanol Metabolism; Expectancy; Exposure to; Feedback; Flushing; Focus Groups; Frequencies; Future; Genes; Genetic; Genotype; Growth; Head and Neck Cancer; Health Promotion; Health behavior; Heavy Drinking; Incentives; Individual; Information Technology; Intervention; Japanese; Knowledge; Lead; Light; Malignant Neoplasms; Malignant neoplasm of esophagus; Mediating; Mediation; Metabolism; Modeling; Names; Online Systems; Outcome; Participant; Pathway interactions; Persons; Phenotype; Prevention; Protocols documentation; Randomized; Reporting; Research; Risk; Risk Behaviors; Role; Sample Size; Sampling; Secure; Self Efficacy; Services; Site; Students; Subgroup; Surveys; Syndrome; Testing; Time; Training; Translating; Universities; Variant; Visit; Work; acetaldehyde dehydrogenase; alcohol expectancy; alcohol involvement; alcohol risk; alcohol use disorder; alcohol use initiation; aldehyde dehydrogenases; attentional control; attenuation; base; behavior change; brief intervention; cancer genetics; cancer prevention; cancer risk; cohort; college; college drinking; comparison group; computerized; design; disorder risk; drinking; drinking onset; early drinking; effective intervention; esophageal squamous cell cancer; experience; genetic risk factor; genetic variant; high risk; high risk population; improved; innovation; insight; intervention effect; men; modifiable behavior; motivational processes; neglect; personalized medicine; physical symptom; pilot test; post intervention; primary outcome; protective allele; recruit; response; scale up; secondary outcome; sex; undergraduate student; university student; web-based intervention

Abstract The primary pathway of alcohol metabolism involves two main enzymes, alcohol and aldehyde dehydrogenase. Several genes (ALDH2, ADH1B) that encode these enzymes have variant alleles that alter the rate of metabolism and result in heightened and protracted exposure to acetaldehyde, a known carcinogen. The variant ALDH2*2 allele is associated with the flushing response (i.e., “Asian glow”) and is found almost exclusively in individuals of east Asian descent (560+ million people worldwide). Although possession of variant ALDH2 and ADH1B alleles are protective against heavy drinking and alcohol use disorders, for those who do drink, these variants also are independently and synergistically associated with striking elevations in risk for several cancers, including esophageal and head and neck cancers. This cancer risk, however, is not widely known outside of the research community. The premise of this study is that we can affect early drinking trajectories through personalized communication about these cancer risks. We specifically target 360 college students of northeast Asian descent, a high-risk group as college is a time of escalating alcohol consumption. It is also a context in which a risk- communications intervention, if successful, could be readily scaled-up. We will compare risk communication with and without personalized genotype feedback by randomizing participants into one of three groups: 1) a group receiving information about cancer risk associated with alcohol consumption and alcohol metabolism genetic deficiencies that manifest as flushing, plus personalized flushing (i.e. phenotype) feedback (PHEN), 2) a group receiving the PHEN information plus personalized genotype feedback on ALDH2 and ADH1B (PHEN+GENE), or 3) a comparison attention CONTROL group receiving duplicate information from the AlcoholEdu® for College mandatory online training about alcohol risk already completed by all incoming students. In Aim 1, we will develop the brief web-based interventions. In Aim 2, we will test our hypotheses that a) informing drinkers of risk will lower alcohol consumption levels and use of “flush cures”, and b) informing non-drinkers will reduce or delay drinking onset. We also will test if genotype feedback results in a greater attenuation of drinking than general risk information and phenotype feedback only, and if the impact is stronger in those at greater risk based on their phenotype and/or genotypes. Finally, we will test the possible mediating roles of perceived cancer risk, cancer prevention self-efficacy, and alcohol expectancies as underlying mechanisms of behavior change. Aim 3 will determine study effect sizes within the latent growth modeling framework we will employ, including for our mediation analyses. These analyses will establish the feasibility of implementing these interventions and setting the stage for a larger multisite study. Results of this work may inform intervention/prevention efforts on how to optimally target personalized feedback protocols for high-risk college samples and scale these at a national level.

抽象的 酒精代谢的主要途径涉及两种主要酶，酒精和醛脱氢酶。 编码这些酶的几种基因（ALDH2，ADH1B）具有改变代谢速率的变异等位基因 并导致乙醛是一种已知的致癌物乙醛。变体ALDH2*2 等位基因与冲洗响应（即“亚洲光芒”）相关，几乎完全在个体中找到 东亚血统（全球560多人）。尽管变体ALDH2和ADH1B的潜力 等位基因受到防止大量饮酒和酒精使用障碍的保护，对于那些喝酒的人，这些变体 也与多种癌症的风险罢工高度相关，也与 食管和头颈部癌症。但是，这种癌症风险在研究之外并不广为人知 社区。这项研究的前提是我们可以通过个性化影响早期的饮酒轨迹 有关这些癌症风险的沟通。我们专门针对东北亚血统的360名大学生， 作为大学的高风险群体是一个不断升级饮酒的时期。这也是风险的背景 如果成功的话，可以轻松扩大通信干预。我们将将风险交流与 没有通过将参与者随机分为三组之一，而没有个性化的基因型反馈：1）一组 接收有关饮酒和酒精代谢仿制药有关的癌症风险的信息 表现为潮红的缺陷，以及个性化的冲洗（即表型）反馈（phen），2）一组 接收PEN信息加上ALDH2和ADH1B（PEN+基因）的个性化基因型反馈， 或3）一个比较注意控制小组，从BOOCHEDU®收到重复的信息 所有新来学生都已经完成了有关酒精风险的强制性在线培训。在AIM 1中，我们将发展 简短的基于Web的干预措施。在AIM 2中，我们将测试我们的假设：a）通知饮酒者的风险 降低酒精消耗水平并使用“冲洗疗法”，b）通知非饮用者将减少或延迟 喝酒。我们还将测试基因型反馈是否会导致饮酒的衰减比一般 风险信息和表型反馈仅限 表型和/或基因型。最后，我们将测试感知到的癌症风险，癌症的介导作用 预防自我效能和酒精期望作为行为改变的潜在机制。目标3意志 确定我们将采用的潜在增长建模框架内的研究效果大小，包括我们 调解分析。这些分析将确定实施这些干预措施并设置的可行性 大型多站点研究的阶段。这项工作的结果可能会为如何进行干预/预防工作。 最佳针对高风险大学样本的个性化反馈方案，并在国家一级扩展这些方案。