Gene x Environment Factors in Smoking Cessation

戒烟的基因 x 环境因素

• 批准号: 6951819
• 负责人: Andrew Hyland
• 金额: $ 53.34万
• 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/6951819
• 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% 的成年人死亡归因于吸烟。戒烟可以大大降低疾病和过早死亡的风险，而提高戒烟率是减少烟草引起的疾病的关键。了解预测戒烟的基因与环境相互作用将有助于进行治疗匹配，以提高戒烟率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，开始吸烟和戒烟的变异性中有 25-50% 是由遗传因素造成的。该提案重点关注三个主要途径（多巴胺、血清素和尼古丁代谢）中的遗传标记，利用从 NCI 戒烟社区试验 (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，是有史以来规模最大的基于社区的吸烟随机试验，因此为分子遗传学研究提供了绝佳的机会。 2001年，7,329名受访者完成了该调查小组的跟踪调查，6,728名受访者同意参与未来的研究。 该项目建议将从所有剩余队列成员邮寄的漱口水样本中获得的 DNA 数据与过去和新收集的吸烟行为、抑郁指标和种族调查数据联系起来，以评估与戒烟相关的基因 x 环境因素。该调查团队帮助启动了 COMMIT 研究，并在多学科烟草研究方面拥有广泛的记录。 我们的主要目的是检查与遗传因素相关的烟草使用模式，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（血清素转运蛋白）和 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并提名其他基因进行分析。结果包括戒烟和复吸、吸烟量以及尼古丁依赖的其他指标。特定的基因与环境相互作用包括遗传标记和抑郁症指标以及检查戒烟结果时药物治疗的利用。第二个目的是分析遗传因素如何通过其他协变量（包括人口统计、过去吸烟行为和烟草控制政策）改变戒烟，并研究遗传因素如何与卷烟产品特征选择相关。