Full Research Project 2 Nicotine Dependence and Lung Cancer Genetics in African Americans

项目总结 全面研究项目2-尼古丁依赖与非裔美国人肺癌遗传学 卡米尔·拉金(Camille Ragin)，博士(Leader)HC：Joel Erblich，博士(Leader) 尽管公共卫生做出了大量的努力来促进戒烟，但在 肺癌的负担依然存在。非洲裔美国人(AA)的肺癌发病率一直较高 与白人相比。值得注意的是，AA吸烟者患肺癌的风险增加，尽管他们 通常每天吸烟的人比白人少。研究表明，肺癌和 尼古丁依赖有很强的家族和遗传成分，以及许多遗传多态。 已被确定为导致发生这些情况的风险的因素。美国存在着巨大的种族差异 已有报道称基因变异与尼古丁代谢有关，并有强有力的初步证据 存在AAs更有可能是烟草烟雾致癌物的不良代谢物，因此容易患上 患肺癌的风险更大。我们将首次系统地探索祖先 参与烟草代谢和成瘾的基因中的信息标记(AIMS)使AA吸烟者容易患上 新陈代谢能力差，对烟草上瘾更大。利用现有的AA吸烟者队列，我们将 1)研究这些目标在烟草新陈代谢和尼古丁依赖中的作用；2)测试 在两个主要城市地区的两个临床和社区样本中，遗传反馈的激励效应： 费城(n=180)和纽约市(n=180)。目标1将假定确定目标之间的关联 与AA烟草代谢和解毒及实际代谢/解毒能力有关 吸烟者，目标2将确定假定与成瘾途径和措施相关的目标之间的关联 AAA吸烟者对尼古丁的依赖，目标3将测试遗传反馈关于 与再生障碍性贫血相关的肺癌风险增加可能会影响感知风险、癌症担忧、急性 心理困扰和戒烟动力。PI具有独特但互补性的领域 具备与吸烟和烟草相关疾病相关的行为和遗传因素方面的专业知识。这个 拟议的研究整合了这两个领域的专业知识，提供跨学科的协同效应，以产生 影响结果，不仅将使调查人员受益，而且有可能为未来的基础、 提高癌症健康公平性的转化和临床研究。由此产生的集体工作 研究将提供新的数据，指导今后调查的两个独特但互补的领域：(A) 促进戒烟者戒烟的量身定制干预措施和(B)机制过程的未来研究 涉及祖先信息遗传标记在烟草相关疾病易感性和 成瘾在再生障碍性贫血中。这项研究将提供一个独特的机会，不仅探索关于 AA吸烟者的肺癌风险遗传学，也支持总体合作和培训目标 在U54上。督导人员将有机会继续合作进行研究和辅导工作，以及 利用他们互补的专业知识来解决及时的、前沿的癌症健康公平问题。

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.