Gene x Environment Factors in Smoking Cessation

戒烟的基因 x 环境因素

• 批准号: 7116457
• 负责人: Andrew Hyland
• 金额: $ 45.05万
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7116457
• 关键词: behavior prediction; behavioral /social science research tag; behavioral genetics; biological signal transduction; bupropion; clinical research; depression; dopamine; drug abuse chemotherapy; drug addiction; drug metabolism; gene environment interaction; gene expression; genetic markers; genetic susceptibility; health behavior; human genetic material tag; human population study; human subject; interview; nicotine; serotonin; smoking cessation

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（由申请人提供）：美国大约20％的成人死亡归因于吸烟。戒烟大大降低了疾病和过早死亡的风险和增加戒烟是减少烟草抗疾病的关键。了解基因X环境的相互作用可以预测戒烟将使治疗匹配增加吸烟戒烟并降低与烟草相关的发病率和死亡率。 烟草依赖性和停止是主要受尼古丁影响的复杂行为。据估计，吸烟开始和戒烟的变异性的25-50％来自遗传因素。该提案着重于三种主要途径（多巴胺，5-羟色胺和尼古丁代谢）中的遗传标记，该数据使用NCI社区试验中的初始参与者收集的数据进行了戒烟（提交），以检查涉及戒烟涉及的遗传和环境因素。始于1988年，COMM是有史以来最大的基于社区的随机试验，因此为分子遗传学研究提供了绝佳的机会。 2001年，有7,329名受访者完成了该调查团队的后续调查，并同意参加未来的研究。 该项目提出了链接从所有剩余的队列成员通过邮件获得的漱口水冲洗样品获得的DNA数据，并具有过去和新收集的有关吸烟行为，抑郁症和种族指标的调查数据，以评估与戒烟有关的基因X环境因素。调查团队帮助启动了该提交研究，并具有多裂烟草研究的广泛记录。 我们的主要目的是检查与遗传因素有关的烟草使用模式，包括以下基因：DRD2和DRD4（多巴胺受体）； SLC6A3（多巴胺转运蛋白）； DBH，COMT，MAOA（多巴胺代谢）； 5-HTT（5-羟色胺转运蛋白），CYP2A6，CYP2B6和CYP2D6（尼古丁代谢）。我们的内部审查以及我们的外部咨询委员会将对其他基因进行审查并提名分析。结果包括戒烟和复发，吸烟数量以及尼古丁依赖性的其他指标。特定的基因X环境相互作用包括遗传标记和抑郁症和药物疗法利用的指标，同时检查停止结果。第二个目的是分析遗传因素如何改变其他协变量的戒烟，包括人口统计学，过去的吸烟行为和烟草控制政策，以及研究如何与烟气产品特征选择相关的遗传因素。