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%的胰腺癌患者死于该疾病。不幸的是，相对较少了解的发病机制和流行病学的恶性肿瘤研究不足。为了解决这一问题，目前的建议侧重于研究胰腺癌的饮食、遗传和生化危险因素。在目标1中，我将研究一种新的饮食指数，该指数可以评估长期全身胰岛素暴露和肥胖和胰岛素抵抗状态下改变的两种激素，脂联素和瘦素。在Aim 2中，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与胰腺癌风险之间的联系。对于Aim 3，我将扩展最近的观察结果，将ABO血型位点的异质性与血浆炎症标志物和胰腺癌风险联系起来。该建议的一个主要优势是能够前瞻性地检查这些因素，从而避免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集之一，建立一个独特的胰腺癌病例和匹配对照数据库，并对数十年来的饮食和生活方式进行反复评估，存档的血液标本和基因组DNA。这个资源将允许我用强大的力量严格检查多个相互关联的途径。此外，它还能让我在新假设出现时快速检验它们。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，并获得经验丰富和成功的临床研究人员的密切，长期的指导，促进我向独立研究者的过渡。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，但我们对这种疾病的易感因素知之甚少。通过目前的建议，我希望能促进我们对胰腺癌发病机制的理解，为评估未来的假设提供重要的资源，并为降低这种高致命性恶性肿瘤的死亡率提供数据支持。

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.