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.

摘要 酒精代谢的主要途径涉及两种主要的酶，酒精和醛脱氢酶。 编码这些酶的几个基因（ALDH 2，ADH 1B）具有改变代谢速率的变异等位基因 并导致对已知致癌物乙醛的高度和长期暴露。变体ALDH 2 *2 等位基因与潮红反应相关（即，“亚洲辉光”），几乎只在个人身上发现 东亚血统（全球5.6亿多人）。虽然携带ALDH 2和ADH 1B变体 等位基因对酗酒和酒精使用障碍有保护作用，对于那些喝酒的人来说，这些变异 也与几种癌症的风险显著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不广为人知 社区这项研究的前提是我们可以通过个性化来影响早期饮酒轨迹 关于这些癌症风险的信息。我们特别针对360名东北亚裔大学生， 大学是一个高风险群体，是一个不断升级的酒精消费时期。这也是一种风险- 传播干预如果成功，很容易扩大规模。我们将风险沟通与 并且没有个性化的基因型反馈，通过将参与者随机分为三组之一： 接受与酒精消费和酒精代谢遗传相关的癌症风险信息 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信息加上关于ALDH 2和ADH 1B的个性化基因型反馈（PHEN+GENE）， 或3）从AlcoholEdu® for College接收重复信息的对照组 所有新生都已经完成了关于酒精风险的强制性在线培训。在目标1中，我们将开发 简短的网络干预。在目标2中，我们将测试我们的假设：a）告知饮酒者风险， 降低酒精消费水平和使用“冲水疗法”，以及B）告知不饮酒者将减少或推迟 酗酒发作我们还将测试基因型反馈是否会导致比一般情况下更大的饮酒衰减 风险信息和表型反馈，如果影响更强，在那些风险更大的基础上， 表型和/或基因型。最后，我们将测试可能的中介作用，感知癌症风险，癌症 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 在我们将采用的潜在增长模型框架内确定研究效应大小，包括我们的 调解分析。这些分析将确定实施这些干预措施的可行性， 为更大规模的多中心研究搭建了舞台。这项工作的结果可以为干预/预防工作提供信息， 最佳针对高风险大学样本的个性化反馈协议，并在全国范围内推广。