Microbiomes in Human Pancreatic Cancer

人类胰腺癌中的微生物组

• 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
• 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

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，胰腺癌是癌症相关死亡的第四大原因，每年导致37,000多人死亡。预后很差，因为大多数胰腺癌在疾病进展晚期才被诊断出来，只有5%的患者在最初诊断后存活了5年。了解胰腺癌的病因对于实施预防措施至关重要，同时可能为如何检测这种高度致命的疾病提供见解。不幸的是，胰腺癌的病因在很大程度上是难以捉摸的，除了消除吸烟和减少肥胖之外，缺乏预防的机会。慢性胰腺炎和炎症被认为在胰腺癌的发生中起关键作用。流行病学研究表明，幽门螺杆菌感染和牙周病会增加患胰腺癌的风险。我们最近报道了牙龈卟啉单胞菌致病性菌株抗体水平高的个体患胰腺癌的风险增加了2倍（OR = 2.38, 95% CI =1.16-4.90，比较bb0 200ng/ml和<200ng/ml）。这些发现强调需要进行基于组织的分析，以充分揭示胰腺癌的多因素微生物特性。因此，我们建议根据我们在人类微生物组计划中的专业知识，检查胰腺癌患者的人类微生物群。我们对胰腺癌组织（新鲜的和石蜡包埋的）的初步研究表明，到目前为止，所有测试的组织中都有高水平的口腔细菌。对于这项建议，我们建议(1)使用最先进的分子技术组合测量胰腺癌患者和未患癌症的受试者的微生物群；(2)检查细菌从口腔传播到胰腺的可能途径。虽然这个项目将无法直接解决因果关系，它将提供