Microbiomes in Human Pancreatic Cancer

人类胰腺癌中的微生物组

基本信息

批准号：
8582772
负责人：
JACQUES G. IZARD
金额：
$ 71.31万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-19 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8582772
关键词：
Address Adenocarcinoma Antibodies Archives Bacteria Biliary Biological Biological Markers Biology Blood Blood specimen Cancer Etiology Cancer Patient Cancerous Cessation of life Cohort Studies Colon Carcinoma Complement Complex Computational Biology Data Data Analyses Detection Development Diagnosis Disease Disease Progression Duct (organ) structure Duodenum Epidemiologic Studies Etiology European Exocrine pancreas Formalin Fresh Tissue Fusobacterium nucleatum Future Genome Goals Health Status Helicobacter Infections Hospitals Human Human Microbiome In Situ Individual Inflammation Institutes Laboratories Lesion Malignant Neoplasms Malignant neoplasm of gastrointestinal tract Malignant neoplasm of pancreas Manuscripts Measures Metabolic Methodology Molecular Nature Obesity Operative Surgical Procedures Oral Oral cavity Pancreas Pancreatic Adenocarcinoma Pancreatic Diseases Pancreatic duct Paraffin Embedding Patients Pattern Periodontal Diseases Periodontitis Pilot Projects Plasma Play Porphyromonas gingivalis Prevention Publications Publishing Recruitment Activity Reporting Rhode Island Risk Role Route Sampling Seminal Specimen Sphincter Staging Techniques Testing Tissue Sample Tissues Tumor Tissue United States National Institutes of Health Universities Work base cancer diagnosis cancer risk carcinogenesis case control chronic pancreatitis cigarette smoking design insight metabolomics method development microbial microbiome migration next generation sequencing oral bacteria outcome forecast pancreatic neoplasm pathogen public health relevance rRNA Genes serological marker tissue fixing

项目摘要

DESCRIPTION (provided by applicant): In the US, pancreatic cancer is the fourth leading cause of cancer-related death and is responsible for over 37,000 annual deaths. Prognosis is poor because most pancreatic cancers are diagnosed late in the progression of the disease, with only 5% of patients alive 5 years after initial diagnosis. Understanding the etiology of pancreatic cancer is critical to implement steps towards prevention and may concurrently provide insights on how to detect this highly fatal disease. Unfortunately, the causes of pancreatic cancer have been largely elusive and other than eliminating cigarette smoking and reducing obesity, opportunities for prevention are absent. Chronic pancreatitis and inflammation are thought to play a critical role in pancreatic carcinogenesis. Epidemiologic studies suggest that Helicobacter pylori infection and periodontal disease increase the risk of pancreatic cancer. We recently reported a 2-fold increase in risk of pancreatic cancer among individuals with high levels of antibodies to a pathogenic strain of Porphyromonas gingivalis (OR = 2.38, 95% CI =1.16-4.90, comparing >200 ng/ml vs. <200ng/ml). These findings underscore the need to perform a tissue based analysis to fully unveil the multifactorial microbial nature of pancreatic cancer. Thus, we propose to examine the human microbiota in pancreatic cancer patients, building from our expertise with the Human Microbiome Project. Our pilot study on pancreatic cancer tissue (fresh and paraffin-embedded) shows high levels of oral bacteria in all tissues tested thus far. For this proposal, we propose to (1) measure microbiota in patients with pancreatic cancer, and in subjects who did not have cancer using a combination of state-of-the-art molecular techniques; (2) examine possible routes of bacteria dissemination from the mouth to the pancreas. While this project will not be able to address causality directly, it will provide valuable data to complement ongoing and future epidemiologic studies examining the role of bacteria in pancreatic cancer. This project is timely and highly relevant to the goals of the NIH Roadmap and the NIH Human Microbiome Project (HMP). Findings from this project will provide key data on the role of bacteria in pancreatic cancer and may provide new opportunities for prevention of this rapidly fatal disease, or for the development of early-stage detection biomarkers.

描述（由申请人提供）：在美国，胰腺癌是与癌症有关的死亡的第四个主要原因，并导致年龄超过37,000人死亡。预后很差，因为大多数胰腺癌在疾病的进展后期都被诊断出来，最初诊断5年后只有5％的患者还活着。了解胰腺癌的病因对于实施预防步骤至关重要，并且可以同时提供有关如何检测这种高度致命疾病的见解。不幸的是，胰腺癌的原因在很大程度上是难以捉摸的，除了消除吸烟和减少肥胖症之外，没有预防机会。慢性胰腺炎和炎症被认为在胰腺癌中起着至关重要的作用。流行病学研究表明，幽门螺杆菌感染和牙周疾病增加了胰腺癌的风险。我们最近报道了对卟啉虫致病性抗体较高抗体的个体的胰腺癌风险增加了2倍（OR = 2.38，95％CI = 1.16-4.90，比较> 200 ng/ml vs. <200ng/ml）。这些发现强调了进行基于组织的分析以完全揭示胰腺癌的多因素微生物性质。因此，我们建议检查胰腺癌患者的人类微生物群，这是根据人类微生物组项目的专业知识来建立的。我们对胰腺癌组织（新鲜和石蜡填充）的试点研究显示，迄今为止所有测试的组织中的口服细菌都很高。对于此提案，我们建议（1）测量胰腺癌患者的微生物群，以及使用最先进的分子技术组合患有癌症的受试者；（2）检查细菌从口腔传播到胰腺的可能路线。虽然该项目将无法直接解决因果关系，但它将提供有价值的数据以补充正在进行的和未来的流行病学研究，以研究细菌在胰腺癌中的作用。该项目与NIH路线图和NIH人类微生物组项目（HMP）的目标及时且高度相关。该项目的发现将提供有关细菌在胰腺癌中作用的关键数据，并可能为预防这种快速致命疾病或发展早期检测生物标志物提供新的机会。