Molecular Epidemiology of Pancreatic Cancer

描述(申请人提供)：本申请100%与个人电脑有关。最近的研究表明，与糖代谢异常相关的因素在PC的发展中起着重要的作用。我们假设胰岛素抵抗(IR)在PC病因学中是一个促进生长的因素。此外，胰岛素、葡萄糖和脂肪代谢以及IR候选基因的遗传变异也与PC风险相关。一项基于临床的病例对照研究将包括从加州大学旧金山分校诊所获得的600名患者和600名对照。访谈期间将收集饮食、体重指数、肥胖症、体力活动、糖尿病和其他因素(包括用药和吸烟)的详细历史。将从符合条件的参与者身上采集血液。加州大学旧金山分校的分子流行病学核心将处理所有血液并提取DMA用于分子/遗传学研究。SNPs将在与IR和代谢以及脂类代谢相关的候选基因中进行检测。基因检测将使用加州大学旧金山分校的基因组核心设施和人员进行。 在样本量允许的情况下，将评估暴露和SNPs的主要影响以及基因-环境和基因-基因的相互作用。我们将与NCI合作开发PC联盟，并将新数据与我们先前基于人口的PC研究(N=2,233)的数据结合起来进行分析。我们将与西雅图和梅奥临床PC研究合作，汇集数据并增加力量，以研究小组中罕见的暴露和因素。主要优势是：1.大量的PC病例将允许按性别、种族和种族进行分析；2.推进PC研究的创新假设(例如SNPs)；3.实验室教职员工和机构的专业知识；4.没有代理访谈；5.基于临床的病例将减少由于生存不良而造成的病例损失；6.对糖尿病、IR、饮食、肥胖、体力活动和SNPs的研究是创新的，对PC的大型研究是新的；7.血液样本将被储存起来，用于未来的基因研究，数据将被汇集起来，以获得更大的统计能力。

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.