Multi-Center Study of Pancreatic Cancer Etiology

描述（由申请人提供）：胰腺癌的风险因素尚未明确。由于其近乎一致和快速的病例死亡率，大多数胰腺癌研究规模较小，应答率适中和/或仅从替代应答者收集数据，并且用于分子分析的生物样本有限（如果有的话）。该项目的长期目标是调查广泛的环境和遗传因素，以提高我们对胰腺癌病因学的理解，首先是基于直接参与者访谈，电子病历审查和血液采样的大型病例对照研究。我们建议进行一项胰腺癌病例对照研究，包括两个健康维护组织（HMO）的规定人群中的745例病例和745例对照，这些组织具有计算机化的管理和临床数据，以支持在诊断后10个工作日内进行“超快速”病例识别。为了最大限度地提高统计功效，以研究不同种族的风险差异，我们将组建第二个对照组，其中296名非裔美国人与预期的74名非裔美国人病例匹配，比例为4：1。 鉴于收集这些数据需要大量的努力，我们提出了一系列广泛的具体目标：1）调查糖尿病和胰腺癌风险之间的关系，重点是糖尿病发病年龄和糖尿病类型，基于访谈和电子病历数据;（二）探讨胰腺癌与饮食的关系，重点关注影响胰岛素抵抗的因素和影响甲基化的因素可用性; 3）研究非甾体类抗炎药的使用与胰腺癌风险的关系4）研究烟草的直接暴露和环境暴露与胰腺癌风险的关系5）研究胰腺癌的家族聚集性;和6）建立研究生物储存库，用于遗传多态性，生物标志物，以及基因与环境的相互作用与胰腺癌风险的关系。这项研究将产生大量新诊断病例的样本，并将为未来的流行病学、分子和遗传学调查建立一个独特而全面的资源。这项研究的结果将导致对胰腺癌风险因素和导致胰腺癌发展的分子事件的更好理解，这对于预防和早期诊断的有效策略都是必要的。

DESCRIPTION (provided by applicant): Risk factors for pancreas cancer are not well established. Because of its near uniform and rapid case fatality, most studies of pancreas cancer have been small, had modest response rates and/or collected data exclusively from a surrogate respondent, and had limited, if any, biologic samples for molecular analysis. The long-term goal of this project is to investigate a wide range of environmental and genetic factors in order to improve our understanding of pancreas cancer etiology, beginning with a large, case-control study based on direct participant interview, electronic medical record review and blood sampling. We propose to conduct a case-control study of pancreas cancer, comprised of 745 cases and 745 controls in the defined populations of two health maintenance organizations (HMO) that have computerized administrative and clinical data to support "ultra-rapid" case identification within ten working days of diagnosis. To maximize statistical power to investigate differences in risk by race, we will assemble a second control group of 296 African-Americans matched to the expected 74 African- American cases using a 4:1 ratio. Given the large effort required to assemble these data, we propose to address an extensive set of specific aims: 1) To investigate the relation between diabetes and pancreas cancer risk, focusing on age at diabetes onset and type of diabetes, based on interview and electronic medical record data; 2) To investigate the relation between pancreas cancer and diet focusing on factors that influence insulin resistance and factors that influence methyl group availability; 3) To investigate the relation between use of non-steroidal anti-inflammatory drugs and pancreas cancer risk; 4) To investigate the relation between direct and environmental exposure to tobacco and pancreas cancer risk; 5) To characterize the familial aggregation of pancreas cancer; and 6) To establish a study biorepository for use in future studies of genetic polymorphisms, biomarkers, and gene-environment interactions in relation to risk of pancreas cancer. The proposed study will result in a large sample of newly diagnosed cases and will establish a unique and comprehensive resource for future epidemiologic, molecular, and genetic investigations. Results from this study will lead to improved understanding of pancreas cancer risk factors and the molecular events leading to the development of pancreas cancer, which are both imperative for effective strategies for prevention and early diagnosis.