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：酒精和乙醛脱氢酶。 编码这些酶的几个基因（ALDH2、ADH1B）具有改变新陈代谢率的变异等位基因 并导致增加和长期接触乙醛（一种已知的致癌物质）。变体 ALDH2*2 等位基因与潮红反应（即“亚洲红”）相关，并且几乎只存在于个体中 东亚裔（全球超过 560 万人）。尽管拥有变体 ALDH2 和 ADH1B 等位基因可以预防酗酒和酒精使用障碍，对于那些喝酒的人来说，这些变体 也与多种癌症风险显着升高独立和协同相关，包括 食道癌和头颈癌。然而，这种癌症风险在研究之外并未广为人知 社区。这项研究的前提是我们可以通过个性化的方式影响早期饮酒轨迹 关于这些癌症风险的沟通。我们专门针对360名东北亚裔大学生， 大学时期是饮酒的高危人群。这也是一个风险的背景 通信干预如果成功，可以很容易地扩大规模。我们将风险沟通与 并且没有将参与者随机分为三组之一的个性化基因型反馈：1）一组 接收有关与饮酒和酒精代谢遗传相关的癌症风险的信息 表现为潮红的缺陷，加上个性化潮红（即表型）反馈（PHEN），2）一组 接收 PHEN 信息以及 ALDH2 和 ADH1B 的个性化基因型反馈 (PHEN+GENE)， 或 3) 比较注意控制组从AlcoholEdu® for College 接收重复信息 所有新生均已完成有关酒精风险的强制性在线培训。在目标 1 中，我们将开发 基于网络的简短干预。在目标 2 中，我们将测试我们的假设：a) 告知饮酒者风险将 降低饮酒量并使用“冲洗疗法”，b) 告知不饮酒者将减少或延迟饮酒 饮酒开始。我们还将测试基因型反馈是否会导致比一般情况更大的饮酒衰减 仅风险信息和表型反馈，并且基于其风险较高的人的影响是否更大 表型和/或基因型。最后，我们将测试感知的癌症风险、癌症的可能中介作用 预防自我效能和酒精预期作为行为改变的潜在机制。目标3将 确定我们将采用的潜在增长模型框架内的研究效果大小，包括我们的 中介分析。这些分析将确定实施这些干预措施和设置的可行性 更大规模的多地点研究的阶段。这项工作的结果可能会为干预/预防工作提供信息，说明如何 针对高风险大学样本优化个性化反馈方案，并在全国范围内进行扩展。