Gene x Environment Factors in Smoking Cessation

戒烟的基因 x 环境因素

• 批准号: 7241446
• 负责人: Andrew Hyland
• 金额: $ 35.41万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-24 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7241446
• 关键词: Address; Adult; Advisory Committees; Alleles; Area; Behavior; Behavioral Genetics; Bupropion/Nicotine; COMT gene; CYP2B6 gene; CYP2D6 gene; Catechol O-Methyltransferase; Cells; Cessation of life; Characteristics; Cigarette; Communities; Community Trial; Complex; Condition; Consent; DNA; DNA Library; DRD2 gene; DRD4 gene; Data; Dependence; Development; Disease; Disease Outcome; Dopamine; Dopamine Receptor; Dopamine-beta-monooxygenase; Environment; Environmental Risk Factor; Ethnic Origin; Future; Genes; Genetic; Genetic Markers; Genetic Predisposition to Disease; Genetic Status; Genetic Variation; Genotype; Intervention; Link; Mails; Mental Depression; Metabolism; Methaqualone; Methods; Molecular Genetics; Morbidity - disease rate; Mouthwash; Nicotine; Nicotine Dependence; Numbers; Outcome; Outcome Study; Participant; Pathway interactions; Patient Self-Report; Pattern; Persons; Pharmacotherapy; Physiological; Policies; Population; Predisposition; Process; Prospective Studies; Randomized; Rate; Relapse; Reporting; Research; Resources; Respondent; Rewards; Role; Saliva; Sampling; Serotonin; Signal Transduction; Smoke; Smoker; Smoking; Smoking Behavior; Surveys; Synapses; System; Testing; Time; Tobacco; Tobacco Dependence; Tobacco Use Cessation; Tobacco use; United States; Vaccines; World Health Organization; attributable mortality; base; behavior influence; burden of illness; cigarette smoking; cohort; cytochrome P-450 CYP2A6 (human); demographics; depressive symptoms; design; disorder risk; dopamine transporter; follow-up; gene environment interaction; genetic analysis; member; mortality; nicotine replacement; programs; public policy on tobacco; research study; serotonin transporter; smoking cessation; tobacco control; transmission process

DESCRIPTION (provided by applicant): Approximately 20% of adult deaths in the U.S. are attributable to cigarette smoking. Smoking cessation greatly reduces the risk of disease and premature death and increasing cessation is key to decreasing tobacco-attributable disease. Understanding gene x environment interactions predictive of smoking cessation would allow for treatment matching to increase smoking cessation and decrease tobacco-related morbidity and mortality. Tobacco dependence and cessation are complex behaviors influenced principally by nicotine. It has been estimated that 25-50% of the variability in smoking initiation and cessation results from genetic factors. This proposal focuses on genetic markers in three prime pathways (dopamine, serotonin, and nicotine metabolism) using data collected from initial participants in the NCI's Community Trial for Smoking Cessation (COMMIT) to examine genetic and environmental factors involved in smoking cessation. Begun in 1988, COMMIT is the largest randomized community-based trial on smoking ever conducted and thus presents an excellent opportunity for molecular genetics studies. In 2001, 7,329 respondents completed this investigative team's follow-up survey and 6,728 consented to participating in future research studies. This project proposes linking DNA data obtained from mouthwash rinse samples obtained through the mail from all remaining cohort members with past and newly collected survey data on smoking behavior, indicators of depression, and ethnicity in order to assess gene x environment factors related to smoking cessation. The investigative team helped initiate the COMMIT study and has an extensive track record of multidiseiplinary tobacco research. Our primary aim is to examine patterns of tobacco use in relation to genetic factors including the following genes: DRD2 and DRD4 (dopamine receptor); SLC6A3 (dopamine transporter); DBH, COMT, MAOA (dopamine metabolism); 5-HTT (serotonin transporter), and CYP2A6, CYP2B6, and CYP2D6 (nicotine metabolism). Additional genes will be reviewed and nominated for analysis by our internal review as well as by our external advisory committee. Outcomes include smoking cessation and relapse, amount smoked, and other indicators of nicotine dependence. Specific gene x environment interactions include genetic markers and indicators of depression and pharmacotherapy utilization while examining cessation outcomes. A secondary aim is to analyze how genetic factors modify smoking cessation by other covariates including demographics, past smoking behavior, and tobacco control policies, as well as to examine how genetic factors may be associated with cigarette product characteristic selection.

描述(申请人提供)：在美国，大约20%的成人死亡可归因于吸烟。戒烟极大地降低了疾病和过早死亡的风险，增加戒烟是减少烟草引起的疾病的关键。了解预测戒烟的基因x环境相互作用将使治疗匹配能够增加戒烟并降低与烟草相关的发病率和死亡率。 烟草依赖和戒烟是主要受尼古丁影响的复杂行为。据估计，在吸烟开始和戒烟过程中，25%-50%的可变性是由遗传因素造成的。这项建议侧重于三个主要途径(多巴胺、5-羟色胺和尼古丁新陈代谢)的遗传标记，使用从NCI的社区戒烟试验(COMMIT)的初始参与者收集的数据来检查与戒烟有关的遗传和环境因素。COMMIT始于1988年，是有史以来进行的最大规模的随机社区吸烟试验，因此为分子遗传学研究提供了一个极好的机会。2001年，7,329名受访者完成了这一调查组的后续调查，6,728名受访者同意参加未来的研究。 该项目建议将通过邮件从所有其余队列成员那里获得的漱口水样本获得的DNA数据与过去和最近收集的关于吸烟行为、抑郁指标和种族的调查数据联系起来，以评估与戒烟相关的基因x环境因素。调查小组帮助启动了承诺研究，并在多学科烟草研究方面拥有广泛的跟踪记录。 我们的主要目的是研究烟草使用模式与遗传因素的关系，包括以下基因：DRD2和DRD4(多巴胺受体)；SLC6A3(多巴胺转运体)；DBH、COMT、MAOA(多巴胺代谢)；5-HTT(5-羟色胺转运体)；以及CYP2A6、CYP2B6和CYP2D6(尼古丁代谢)。我们的内部审查以及外部咨询委员会将审查和提名更多的基因进行分析。结果包括戒烟和复发、吸烟量和尼古丁依赖的其他指标。在检查戒烟结果时，特定的基因x环境交互作用包括遗传标记和抑郁症和药物治疗利用的指标。第二个目的是分析遗传因素如何通过其他协变量影响戒烟，包括人口统计学、过去的吸烟行为和烟草控制政策，以及研究遗传因素如何与卷烟产品特性选择相关。

项目成果

Alpha-5 and -3 nicotinic receptor gene variants predict nicotine dependence but not cessation: findings from the COMMIT cohort.

• DOI: 10.1002/ajmg.b.32019
• 发表时间: 2012-03
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
• 影响因子: 2.8
• 作者: Bousman, Chad A.;Rivard, Cheryl;Den Haese, Jason;Ambrosone, Christine;Hyland, Andrew
• 通讯作者: Hyland, Andrew