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.

项目摘要肺癌是美国癌症死亡的主要原因，与非洲裔美国人（AAS）出于不良的原因，患肺癌的发病率要高理解。最近的研究表明，肺部由各种类型的社区居住细菌和肺中的细菌感染与肺癌风险有关。最近的研究还表明，口服微生物组是肺中细菌菌群的主要来源，并且肺的细菌群落重叠了在口腔中发现的细菌群落。我们在试点研究中发现多个口腔冲洗样品中的细菌类群与肺癌风险有关。我们假设（1）口头微生物组可能在肺癌病因中起作用，（2）口服细菌可能与香烟相互作用吸烟和慢性肺疾病会影响肺癌风险，（3）AAS的口服微生物组可能不同从欧洲人（EA）的方式中，可能导致AAS肺癌发病率很高。到检验这些假设，我们将使用已经收集的数据并存储了来自南部的生物测量社区队列研究（SCC）和黑人妇女健康研究（BWHS）。口冲洗样品是使用类似收集方法。在拟议的研究中，我们将对肺癌进行嵌套的病例对照研究，其中800个事件案件（600 AA和200 EAS）和1,000个匹配的对照（600 AA和400 EA），使用前诊断口冲洗样品。我们将执行整个元基因组shot弹枪测序并使用高级生物统计学和生物信息学技术研究口服微生物组成（细菌/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）他们与肺癌风险的关联（AIM 1）。我们将评估口服微生物的可能相互作用与肺癌风险有关的其他风险因素的社区（AIM 2）。我们将进一步评估是否 AAS和EAS之间的口服微生物组和肺癌协会以及非洲血统是否有所不同修改微生物肺癌的关联（AIM 3）。最后，我们将进行体外研究以评估鉴定细菌的潜在功能（AIM 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和肺癌风险之间关联的研究。异常 SCC和BWH的资源，再加上最先进的整个Metagenome shot弹枪测序和生物信息学技术，提供了一个空前的机会来评估口服微生物组的作用在肺癌风险中。我们拟议的研究的结果将增加对病理生理学的理解微生物组对肺癌病因的影响，可以为预防性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。