Microbiomes in Human Pancreatic Cancer

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，每年造成超过37，000例死亡。预后很差，因为大多数胰腺癌在疾病进展的晚期被诊断出来，只有5%的患者在初次诊断后存活5年。了解胰腺癌的病因对于实施预防措施至关重要，同时可以提供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，预防的机会是不存在的。慢性胰腺炎和炎症被认为在胰腺癌发生中起关键作用。流行病学研究表明，幽门螺杆菌感染和牙周病会增加胰腺癌的风险。我们最近报道，在牙龈卟啉单胞菌致病菌株抗体水平高的个体中，胰腺癌的风险增加2倍（OR = 2.38，95%CI =1.16-4.90，比较>200 ng/ml与<200 ng/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性质。因此，我们建议研究胰腺癌患者的人类微生物群，以我们在人类微生物组项目中的专业知识为基础。我们对胰腺癌组织（新鲜和石蜡包埋）的初步研究显示，迄今为止，所有测试组织中的口腔细菌水平都很高。对于这项提议，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。虽然这个项目不能直接解决因果关系，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，检查细菌在胰腺癌中的作用。该项目是及时的，与NIH路线图和NIH人类微生物组项目（HMP）的目标高度相关。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的疾病或开发早期检测生物标志物提供新的机会。

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.