Cohort Study of Biochemical and Genetic Risk Factors for Pancreatic Cancer

描述（由申请人提供）：胰腺癌是美国癌症相关死亡的第四大原因，95%的胰腺癌患者死于胰腺癌。不幸的是，相对知之甚少的发病机制和流行病学，这种研究不足的恶性肿瘤。为了解决这一问题，目前的建议侧重于调查饮食，遗传和生化风险因素的胰腺癌。对于目标1，我将研究一种新的饮食指数，估计长期全身胰岛素暴露和两种激素改变的肥胖和胰岛素抵抗状态，脂联素和瘦素。对于目标2，我将研究炎症、幽门螺杆菌感染和端粒长度的血浆标志物，以更好地了解慢性炎症和胰腺癌风险之间的联系。对于目标3，我将扩展最近的观察，将ABO血型位点的异质性与血浆炎症标志物和胰腺癌的风险联系起来。该建议的主要优点是能够前瞻性地检查这些因素，从而避免了与胰腺癌流行病学回顾性分析相关的问题。此外，该提案将汇集迄今为止最大的前瞻性病例对照组之一，建立胰腺癌病例和匹配对照的独特数据库，数十年来重复饮食和生活方式评估，存档血液标本和基因组DNA。这个资源将使我能够严格检查多个相互关联的途径与强大的力量。此外，它将使我能够迅速检查新的假设，因为他们出现。最后，这个奖项将使我能够发展生物统计学和流行病学的高级技能，追求胰腺癌研究的重点项目，并从经验丰富和成功的临床研究人员那里获得密切，长期的指导，促进我向独立研究者的转变。相关性：虽然胰腺癌是美国癌症相关死亡的第四大常见原因，我们对这种疾病的诱发因素知之甚少。通过目前的提议，我希望能促进我们对胰腺癌发病机制的理解，产生一个重要的资源来评估未来的假设，并提供数据来支持降低这种高致命性恶性肿瘤死亡率的建议。

DESCRIPTION (provided by applicant): Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States, and 95% of patients who develop pancreatic cancer die from their disease. Unfortunately, relatively little is known about the pathogenesis and epidemiology of this under-studied malignancy. To address this problem, the current proposal focuses on the investigation of dietary, genetic and biochemical risk factors for pancreatic cancer. For Aim 1, I will examine a novel dietary index that estimates long-term systemic insulin exposure and two hormones altered in states of obesity and insulin resistance, adiponectin and leptin. For Aim 2, I will investigate plasma markers of inflammation, Helicobacter pylori infection, and telomere length, in an effort to better understand the link between chronic inflammation and, pancreatic cancer risk. For Aim 3, I will expand on recent observations linking heterogeneity at the ABO blood group locus with plasma inflammatory markers and the risk of pancreatic cancer. A major strength of this proposal is the ability to examine these factors prospectively, thereby avoiding the problems associated with retrospective analyses of pancreatic cancer epidemiology. Moreover, this proposal will assemble one of the largest prospective case-control sets to date, establishing a unique database of pancreatic cancer cases and matched controls, with repeated dietary and lifestyle assessments over several decades, archived blood specimens, and genomic DNA. This resource will allow me to rigorously examine multiple inter-related pathways with robust power. In addition, it will allow me to rapidly examine new hypotheses as they emerge. Finally, this award will enable me to develop advanced skills in biostatistics and epidemiology, pursue a focused program in pancreatic cancer research, and receive close, long-term mentorship from experienced and successful clinical researchers, promoting my transition to an independent investigator. RELEVANCE: Although pancreatic cancer is the 4th most common cause of cancer-related death in the U.S., we know little about predisposing factors for this disease. With the current proposal, I hope to advance our understanding of pancreatic cancer pathogenesis, generate an important resource to evaluate future hypotheses, and provide data to support recommendations for reducing mortality from this highly lethal malignancy.