Nicotine Dependence and Lung Cancer Genetics in African Americans

非裔美国人的尼古丁依赖和肺癌遗传学

• 批准号: 10015226
• 负责人: Camille C. Ragin
• 金额: $ 20.79万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-19 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10015226
• 关键词: Acute; Address; Adult; African; African American; American; Area; Asians; Basic Science; Behavioral Genetics; Biological; Biological Factors; Cancer Etiology; Carcinogens; Cigarette; Clinical; Clinical Research; Cognitive; Collaborations; Communities; Data; Dependence; Development; Disease; Disease susceptibility; Doctor of Philosophy; Drug Metabolic Detoxication; European; Exhibits; Feedback; Foundations; Future; General Population; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Risk; Health behavior outcomes; Incidence; Intervention; Investigation; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Mentors; Metabolic; Metabolism; Motivation; New York City; Nicotine; Nicotine Dependence; Pathway interactions; Perception; Persons; Philadelphia; Population; Predisposition; Process; Prospective Studies; Public Health; Race; Reporting; Reproducibility of Results; Research; Research Personnel; Research Project Grants; Resolution; Risk; Risk Marker; Role; Sampling; Services; Site; Smoke; Smoker; Smoking; Smoking Behavior; Smoking Cessation Intervention; Testing; Time; Tobacco; Tobacco Dependence; Tobacco smoke; Tobacco use; Training; Translational Research; United States; Variant; Work; addiction; base; cancer genetics; cancer health disparity; cancer risk; cigarette smoking; clinical center; cohort; emotional behavior; genetic association; genetic information; genetic variant; health care availability; health equity; mortality; novel; psychological distress; racial difference; smoking cessation; socioeconomics; synergism; urban area

PROJECT SUMMARY Full Research Project 2 - Nicotine Dependence and Lung Cancer Genetics in African Americans TUFCCC: Camille Ragin, PhD (Leader) HC: Joel Erblich, PhD (Leader) Despite substantial public health efforts to promote smoking cessation, a significant racial difference in the burden of lung cancer persists. African Americans (AA) consistently have a higher incidence of lung cancer compared to Whites. Notably, AA smokers are at increased risk of lung cancer despite the fact that they typically smoke fewer cigarettes per day than Whites. Research has demonstrated that both lung cancer and nicotine dependence have strong familial and genetic components, and numerous genetic polymorphisms have been identified as contributing to risk of developing these conditions. Substantial racial differences in the association of genetic variants with nicotine metabolism have been reported and strong preliminary evidence exists that AAs are more likely to be poor metabolizers of tobacco smoke carcinogens, thus predisposed to greater risk of developing lung cancer. We will, for the first time, systematically explore whether ancestry informative markers (AIMs) in genes involved in tobacco metabolism and addiction predispose AA smokers to poor metabolic capacity and greater addiction to tobacco. Leveraging an existing cohort of AA smokers, we will 1) investigate the role of these AIMs in both tobacco metabolism and nicotine dependence and 2) test the motivational effects of genetic feedback, in two clinical and community samples in two major urban areas: Philadelphia (n=180) and New York City (n=180). Aim 1 will identify associations between AIMs putatively related to the tobacco metabolism and detoxification and actual metabolic/detoxification capacity in AA smokers, Aim 2 will identify associations between AIMs putatively related to addiction pathways and measures of nicotine dependence among AA smokers, and Aim 3 will test the possibility that genetic feedback about increased lung cancer risk associated with AA ancestry may influence perceived risk, cancer worry, acute psychological distress, and motivation to quit smoking. The PIs have unique, yet complementary areas of expertise in behavioral and genetic factors associated with cigarette smoking and tobacco-related disease. The proposed study integrates both of these areas of expertise, providing interdisciplinary synergy to yield high impact results that will not only benefit the investigators, but will have the potential to inform future basic, translational, and clinical research on enhancing cancer health equity. The collective work generated by this study will provide novel data that will guide two unique, but complementary, areas of future investigation: (a) a tailored intervention to promote smoking cessation among AA and (b) future studies of mechanistic processes involving the role of ancestry informative genetic markers in tobacco-related disease susceptibility and addiction in AA. This study will provide a unique opportunity, not only to explore novel hypotheses about the genetics of lung cancer risk in AA smokers, but also to support the overall collaboration and training objectives of the U54. The PIs will have the opportunity to continue their research and mentoring work collaboratively, and leverage their complementary expertise to address timely, cutting-edge questions of cancer health equity.

项目概要 完整研究项目 2 - 非裔美国人的尼古丁依赖和肺癌遗传学 TUFCCC：Camille Ragin，博士（领导者） HC：Joel Erblich，博士（领导者） 尽管公共卫生部门为促进戒烟做出了大量努力，但吸烟者之间仍存在显着的种族差异。 肺癌的负担依然存在。非裔美国人 (AA) 的肺癌发病率始终较高 与白人相比。值得注意的是，尽管 AA 吸烟者患肺癌的风险增加，但他们 通常每天吸烟的数量比白人少。研究表明，肺癌和 尼古丁依赖具有很强的家族和遗传成分，以及许多遗传多态性 已被确定为导致这些病症发生的风险的因素。种族差异显着 遗传变异与尼古丁代谢的关联已被报道，并且有强有力的初步证据 存在的事实是，AA 更有可能是烟草烟雾致癌物的不良代谢者，因此容易 患肺癌的风险更大。我们将首次系统地探讨祖先是否 与烟草代谢和成瘾有关的基因中的信息标记（AIM）使 AA 吸烟者倾向于 新陈代谢能力差，对烟草的依赖性更大。利用现有的 AA 吸烟者群体，我们将 1) 研究这些 AIM 在烟草代谢和尼古丁依赖中的作用，2) 测试 遗传反馈的动机效应，在两个主要城市地区的两个临床和社区样本中： 费城 (n=180) 和纽约市 (n=180)。目标 1 将识别 AIM 之间的关联 与烟草代谢和解毒以及 AA 中的实际代谢/解毒能力有关 吸烟者，目标 2 将确定与成瘾途径和措施相关的 AIM 之间的关联 AA 吸烟者中尼古丁依赖的影响，目标 3 将测试遗传反馈的可能性 与 AA 血统相关的肺癌风险增加可能会影响感知风险、癌症担忧、急性 心理困扰和戒烟动机。 PI 具有独特但互补的领域 与吸烟和烟草相关疾病相关的行为和遗传因素的专业知识。这 拟议的研究整合了这两个专业领域，提供跨学科协同作用，以产生高成果 影响结果不仅有利于研究人员，而且有可能为未来的基础、 增强癌症健康公平性的转化和临床研究。由此产生的集体工作 研究将提供新颖的数据，指导未来研究的两个独特但互补的领域：(a) 促进 AA 戒烟的定制干预措施以及 (b) 未来的机制过程研究 涉及祖先信息遗传标记在烟草相关疾病易感性中的作用和 AA 成瘾。这项研究将提供一个独特的机会，不仅可以探索关于 AA 吸烟者肺癌风险的遗传学，同时也支持总体合作和培训目标 U54的。 PI 将有机会继续合作研究和指导工作，并且 利用他们互补的专业知识及时解决癌症健康公平的前沿问题。