Oral Microbiome and Lung Cancer Risk

项目摘要 肺癌是美国癌症死亡的主要原因，非裔美国人(AA) 罹患肺癌的比例比其他任何民族或种族都要高，原因也不多。 明白了。最近的研究表明，肺部居住着不同类型的 细菌和肺部的细菌感染与肺癌风险有关。最新研究 还表明，口腔微生物群是肺部细菌微生物群的主要来源，而 肺部的细菌群落与口腔中的细菌群落重叠。我们在初步研究中发现，有多个 漱口水样本中的细菌分类群与肺癌风险相关。我们假设(1)口述 微生物群可能在肺癌的病因中发挥作用，(2)口腔细菌可能与香烟相互作用 吸烟和慢性肺部疾病对肺癌风险的影响，以及(3)AAs的口腔微生物群可能不同 与欧洲美国人(EAs)不同，这可能会导致AA肺癌的高发病率。至 测试这些假设，我们将使用已经收集的数据和从南方 社区队列研究(SCCS)和黑人妇女健康研究(BWHS)。漱口水样本是 收集自大约39,000名SCCS参与者和28,000名BWHS参与者，使用类似的 收集方法。在拟议的研究中，我们将进行一项关于肺癌的嵌套病例对照研究，共有800人 事故案例(600个AA和200个EA)和1,000个匹配对照(600个AA和400个EA)，使用PRE 诊断性含漱液样本。我们将执行整个超基因组鸟枪式测序，并使用高级 用生物统计学和生物信息学技术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) 它们与肺癌风险的关系(目标1)。我们将评估口腔微生物可能的相互作用 具有与肺癌风险有关的其他危险因素的社区(目标2)。我们会进一步评估是否会 口腔微生物群与肺癌的相关性在AAs和EAs之间以及非洲血统之间是否存在差异 修改微生物组-肺癌协会(目标3)。最后，我们将进行体外研究，以评估 已确定细菌的潜在功能(目标4)。这项拟议的研究具有很高的创新性，因为没有 已发表的关于口腔微生物群与肺癌风险之间关系的研究。不同寻常的 SCCS和BWHS的资源，加上最先进的全基因组鸟枪测序和 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 有患肺癌的风险。我们建议的研究结果将增加对病理生理学的理解。 微生物群在肺癌病因学中的作用并可为预防提供有用的信息 此外，还提供了新的信息，以改善肺癌患者之间的差异。

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.