Oral Microbiome and Lung Cancer Risk

项目摘要 肺癌是美国癌症死亡的主要原因，非洲裔美国人（AAs） 肺癌的发病率高于任何其他种族或种族群体，原因是 明白最近的研究表明，肺部居住着各种类型的社区， 肺部的细菌感染与肺癌风险有关。最近的研究 还表明，口腔微生物组是肺部细菌微生物群的主要来源， 肺部的细菌群落与口腔中的细菌群落重叠。我们在试点研究中发现， 漱口液样本中的细菌分类群与肺癌风险相关。我们假设（1）口服 微生物组可能在肺癌的病因学中起作用，（2）口腔细菌可能与香烟相互作用 吸烟和慢性肺部疾病影响肺癌风险，以及（3）AA的口腔微生物组可能不同 与欧洲裔美国人（EAs）的差异可能导致AAs肺癌的高发病率。到 为了验证这些假设，我们将使用已经收集的数据和储存的生物标本， 社区队列研究（SCCS）和黑人妇女健康研究（BWHS）。漱口水样本为 使用类似的方法从大约39，000名SCCS参与者和28，000名BWHS参与者中收集 收集方法在拟议的研究中，我们将进行肺癌的巢式病例对照研究， 事件病例（600例AA和200例EA）和1，000例匹配对照（600例AA和400例EA），使用前 诊断用漱口水样品。我们将进行整个宏基因组鸟枪测序，并使用先进的 生物统计学和生物信息学技术来研究口腔微生物组成（细菌种类/菌株 丰度和多样性）和功能能力（细菌基因/途径丰度和多样性） 与肺癌风险的关系（目标1）。我们将评估口腔微生物之间可能的相互作用， 与肺癌风险相关的其他风险因素的社区（目标2）。我们将进一步评估 口腔微生物组与肺癌的关联在AA和EA之间存在差异， 改变微生物组-肺癌关联（Aim 3）。最后，我们将进行体外研究， 鉴定细菌的潜在功能（目的4）。这项研究极具创新性，因为没有 发表了关于口腔微生物组与肺癌风险之间关系的研究。的特殊 SCCS和BWHS的资源，加上最先进的全宏基因组鸟枪测序， 生物信息学技术为评估口腔微生物组的作用提供了前所未有的机会 肺癌的风险。我们提出的研究结果将增加对病理生理学的理解， 微生物组在肺癌病因学中的作用，可为预防肺癌提供有用的信息。 干预措施以及提供新的信息，以改善肺癌的差异。

Project Summary Lung cancer is the leading cause of cancer death in the United States, with African Americans (AAs) suffering a higher lung cancer incidence than any other ethnic or racial group, for reasons that are poorly understood. Recent studies have shown that the lungs are inhabited by communities of diverse types of bacteria and that bacterial infection in the lungs has been associated with lung cancer risk. Recent studies have also shown that the oral microbiome is the primary source of bacterial microbiota in the lungs and that the bacterial communities of the lungs overlap those found in the mouth. We found in our pilot study that multiple bacterial taxa in mouth rinse samples were associated with lung cancer risk. We hypothesize that (1) oral microbiomes may play a role in the etiology of lung cancer, (2) oral bacteria may interact with cigarette smoking and chronic lung diseases to influence lung cancer risk, and (3) the oral microbiome of AAs may differ from that of European Americans (EAs) in ways that could lead to a high incidence of lung cancer in AAs. To test these hypotheses, we will use already collected data and stored biospecimens from the Southern Community Cohort Study (SCCS) and Black Women's Health Study (BWHS). Mouth rinse samples were collected from approximately 39,000 SCCS participants and 28,000 BWHS participants using a similar collection method. In the proposed study, we will conduct a nested case-control study of lung cancer, with 800 incident cases (600 AAs and 200 EAs) and 1,000 matched controls (600 AAs and 400 EAs), using pre- diagnostic mouth rinse samples. We will perform whole metagenome shotgun sequencing and use advanced biostatistics and bioinformatics techniques to investigate oral microbial composition (bacterial species/strains abundance and diversity) and functional capabilities (bacterial genes/pathways abundance and diversity) for their associations with lung cancer risk (Aim 1). We will evaluate the possible interaction of oral microbial communities with other risk factors in relation to lung cancer risk (Aim 2). We will further evaluate whether the oral microbiome and lung cancer association differs between AAs and EAs and whether African ancestry modifies the microbiome-lung cancer association (Aim 3). Finally, we will perform in vitro studies to evaluate potential function of identified bacteria (Aim 4). The proposed study is highly innovative, as there are no published studies on the association between the oral microbiome and lung cancer risk. The exceptional resources of the SCCS and BWHS, coupled with state-of-the-art whole metagenome shotgun sequencing and bioinformatics technologies, provide an unprecedented opportunity to evaluate the role of the oral microbiome in lung cancer risk. Results from our proposed study will increase understanding of the pathophysiological effects of microbiomes on the etiology of lung cancer and could provide useful information for preventive interventions as well as providing new information to ameliorate disparities in lung cancer.