Nicotine Dependence and Lung Cancer Genetics in African Americans

项目摘要 完整的研究项目2 -尼古丁依赖和肺癌遗传学在非洲裔美国人 TUFCCC：Camille Ragin，PhD（Leader）HC：Joel Erblich，PhD（Leader） 尽管大量的公共卫生工作，以促进戒烟，一个显着的种族差异， 肺癌的负担仍然存在。非裔美国人（AA）一直有较高的肺癌发病率 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 通常每天吸烟比白人少。研究表明，肺癌和 尼古丁依赖具有很强的家族性和遗传性，以及许多遗传多态性 已被确定为导致这些疾病的风险。种族间的巨大差异 已经报道了遗传变异与尼古丁代谢的关联， 存在AA更可能是烟草烟雾致癌物的弱代谢物，因此易于 患肺癌的风险更大。我们将第一次系统地探讨祖先是否 参与烟草代谢和成瘾的基因中的信息标记（AIM）使AA吸烟者易于 新陈代谢能力差，对烟草上瘾。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 遗传反馈的激励作用，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将确定目标之间的联系， 与烟草的代谢和解毒以及AA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 Aim 3将测试AA吸烟者对尼古丁依赖的遗传反馈的可能性， 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 心理压力和戒烟的动机。PI具有独特但互补的领域， 在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。的 拟议的研究整合了这两个领域的专业知识，提供跨学科的协同作用，以产生高 影响结果，不仅将有利于研究人员，但将有可能告知未来的基本， 促进癌症健康公平性的转化和临床研究。由此产生的集体工作 这项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： 在AA中促进戒烟的量身定制的干预和（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， 在AA成瘾。这项研究将提供一个独特的机会，不仅探索新的假设， AA吸烟者肺癌风险的遗传学，而且还支持整体合作和培训目标 关于U 54 PI将有机会继续合作开展研究和指导工作， 利用其互补的专业知识，及时解决癌症健康公平的前沿问题。

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.