Multi-Center Study of Pancreatic Cancer Etiology

描述(由申请人提供)：胰腺癌的危险因素尚未完全确定。由于其近乎一致和快速的病死率，大多数胰腺癌研究规模较小，应答率适中和/或仅从替代受试者那里收集数据，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的理解，首先是一项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。我们建议对胰腺癌进行一项病例对照研究，包括两个健康维护组织(HMO)确定的人群中的745例病例和745名对照，这两个组织已将管理和临床数据计算机化，以支持在诊断后10个工作日内进行“超快速”病例识别。为了最大限度地利用统计学力量调查不同种族之间的风险差异，我们将以4：1的比例召集另一个由296名非洲裔美国人组成的对照组，与预期的74例非洲裔美国人病例相匹配。 考虑到收集这些数据所需的大量努力，我们建议解决一系列具体目标：1)基于访谈和电子病历数据，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；2)调查胰腺癌与饮食的关系，重点是影响胰岛素抵抗的因素和影响甲基可获得性的因素；3)调查非类固醇抗炎药的使用与胰腺癌风险的关系；4)调查直接接触烟草和环境暴露与胰腺癌风险的关系；5)描述胰腺癌的家族聚集性；以及6)建立研究生物信息库，用于未来与胰腺癌风险相关的遗传多态、生物标记物和基因-环境相互作用的研究。拟议的研究将导致新诊断病例的大样本，并将为未来的流行病学、分子和遗传学调查建立一个独特和全面的资源。这项研究的结果将有助于更好地了解胰腺癌的危险因素和导致胰腺癌发展的分子事件，这对于有效的预防和早期诊断都是必不可少的。

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.