Molecular Epidemiology of Pancreatic Cancer

描述（由申请人提供）：本申请100%与PC相关。最近的研究表明，与糖代谢异常相关的因素在PC的发展中是重要的。我们假设胰岛素抵抗（IR）是PC病因学中的生长促进因素。此外，胰岛素、葡萄糖和脂质代谢以及IR候选基因的遗传变异与PC风险相关。一项基于临床的病例对照研究将包括从UCSF诊所获得的600名患者和600名对照。访谈期间将收集饮食、体重指数、肥胖、体力活动、糖尿病和其他因素（包括药物使用和吸烟）的详细历史。将采集合格受试者的血液。加州大学旧金山分校的分子流行病学核心将处理所有的血液和提取DMA用于分子/遗传研究。将在与IR和代谢以及脂质代谢相关的候选基因中检查SNP。基因检测将使用UCSF的基因组核心设施和人员进行。 当样本量允许时，将评价暴露和SNP的主要影响以及基因-环境和基因-基因相互作用。我们将与NCI合作开发PC联盟，并将联合收割机新数据与我们早期基于人群的PC研究（N= 2，233）的数据结合起来进行分析。我们将与西雅图和马约诊所PC研究合作，以汇集数据并增加研究小组内罕见暴露和因素的能力。主要优势是：1.大量PC病例将允许按性别、种族和人种进行分析; 2.创新的假设，以推进PC研究（如SNPs）; 3。实验室教师和设施的专业知识; 4。没有代理面试; 5.基于临床的病例将减少由于生存率差而导致的病例丢失; 6.糖尿病、IR、饮食、肥胖、体力活动和SNP的研究对于PC的大型研究是创新的和新的; 7.血液样本将被储存用于未来的遗传研究，数据将被合并以获得更大的统计功效。

DESCRIPTION (provided by applicant): This application is 100% related to PC. Recent studies show that factors associated with abnormal glucose metabolism are important in PC development. We hypothesize that insulin resistance (IR) is a growth-promoting factor in PC etiology. Also, genetic variation in insulin, glucose, and lipid metabolism and in candidate genes for IR are related to PC risk. A clinic-based case-control study will include 600 patients and 600 controls obtained from UCSF clinics. Detailed history of diet, body mass index, obesity, physical activity, diabetes and other factors including medication use and smoking will be collected during interviews. Blood will be collected from eligible participants. UCSF's Molecular Epidemiology Core will process all bloods and extract DMA for use in molecular/ genetic studies. SNPs will be examined in candidate genes related to IR and metabolism, and lipid metabolism. Genetic testing will be done using UCSF's Genome Core facilities and personnel. Main effects for exposures and SNPs will be evaluated as will gene-environment and gene-gene interactions when sample sizes permit. We will work with NCI on the PC consortium development and combine new data with data from our earlier population-based PC study (N=2,233) to conduct analyses. We will collaborate with Seattle and Mayo clinic PC studies to pool data and increase power to study rare exposures and factors within small groups. Major strengths are: 1. Large number of PC cases will allow analyses by sex, ethnicity and race; 2. Innovative hypotheses to advance PC research (e.g. SNPs); 3. Expertise of lab faculty and facilities; 4. No proxy interviews; 5. Clinic-based cases will diminish case loss due to poor survival; 6. Studies of diabetes, IR, diet, obesity, physical activity and SNPs are innovative and new to large studies of PC; 7. Blood samples will be banked for future genetic studies and data will be pooled for greater statistical power.