Oral Microbiome and Lung Cancer Risk

口腔微生物组和肺癌风险

基本信息

批准号：
9160365
负责人：
QIUYIN CAI
金额：
$ 67.5万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9160365
关键词：
Acute respiratory infection Adult Affect African African American American Bacteria Bacterial Genes Bacterial Infections Bioinformatics Biometry Cancer Etiology Cancer cell line Cell Proliferation Cessation of life Chlamydophila pneumoniae Chronic Chronic Disease Chronic Obstructive Airway Disease Chronic lung disease Cohort Studies Collection Communities Coupled Data Diagnostic Epithelial Cells Ethnic group Etiology European Immune system In Vitro Incidence Infection Inflammation Investigation Lead Life Style Light Lung Lung diseases Malignant Neoplasms Malignant neoplasm of lung Meta-Analysis Methods Mouth Diseases Nested Case-Control Study Nitrosamines Odds Ratio Oral Oral cavity Oral health Participant Pathway interactions Patients Pilot Projects Play Pneumonia Predisposition Preventive Intervention Public Health Publishing Race Recording of previous events Reporting Resources Risk Risk Factors Role Sampling Shotgun Sequencing Smoking Source Taxon Techniques Technology Testing Tissue Sample Tobacco smoking Tooth Loss Tuberculosis Tumor Tissue United States Woman Women&apos s Health cancer risk cigarette smoking innovation lung carcinogenesis men metagenome microbial microbial community microbiome microbiota next generation sequencing oral bacteria oral microbiome population based prospective racial disparity

项目摘要

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.

项目概要肺癌是美国非裔美国人 (AA) 癌症死亡的主要原因肺癌发病率高于任何其他民族或种族群体，但原因尚不清楚明白了。最近的研究表明，肺部居住着不同类型的微生物群落。细菌，肺部细菌感染与肺癌风险相关。最近的研究还表明，口腔微生物群是肺部细菌微生物群的主要来源，并且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，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) 口头微生物组可能在肺癌的病因学中发挥作用，（2）口腔细菌可能与香烟相互作用吸烟和慢性肺部疾病会影响肺癌风险，并且 (3) AA 的口腔微生物组可能有所不同与欧洲裔美国人 (EA) 不同，这可能导致 AA 中肺癌的高发病率。到检验这些假设，我们将使用已经收集的数据和来自南方的生物样本社区队列研究 (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 参与者收集采集方法。在拟议的研究中，我们将进行一项肺癌的巢式病例对照研究，其中 800 事件案例（600 个 AA 和 200 个 EA）和 1,000 个匹配对照（600 个 AA 和 400 个 EA），使用预诊断漱口水样本。我们将进行整个宏基因组鸟枪测序并使用先进的研究口腔微生物组成（细菌种类/菌株）的生物统计学和生物信息学技术丰度和多样性）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联（目标 1）。我们将评估口腔微生物可能的相互作用存在与肺癌风险相关的其他风险因素的社区（目标 2）。我们将进一步评估是否口腔微生物组与肺癌的关联在 AA 和 EA 之间存在差异，以及非洲血统是否存在差异改变微生物组与肺癌的关联（目标 3）。最后，我们将进行体外研究来评估已识别细菌的潜在功能（目标 4）。拟议的研究具有高度创新性，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。非凡的 SCCS 和 BWHS 的资源，加上最先进的全宏基因组鸟枪法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肺癌风险。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对肺癌病因学的影响，可以为预防提供有用的信息干预措施以及提供新信息以改善肺癌的差异。