Prospective Cohort Collaborative in Pancreatic Cancer Epidemiology & Pathogenesis

胰腺癌流行病学前瞻性队列合作

基本信息

批准号：
8137000
负责人：
CHARLES S FUCHS
金额：
$ 74.67万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-23 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8137000
关键词：
25-hydroxyvitamin D American Analgesics Archives Behavior Biological Markers C-Peptide C-reactive protein Cancer Biology Cancer Etiology Cholecalciferol Cohort Studies Collaborations Coupled Data Data Analyses Databases Development Diet Dietary Factors Dose Epidemiology Fasting Functional disorder Future GC gene Gene Cluster Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Variation Grant Health Health Professional Helicobacter pylori Hormonal Hormones Hyperinsulinism Incidence Individual Inflammation Inflammatory Insulin Insulin Resistance Intake Interleukin-10 Interleukin-6 Life Style Malignant Neoplasms Malignant neoplasm of pancreas Mediating Methods Molecular NIH Program Announcements Nurses&apos Health Study Nutrient Obesity Pancreas Pathogenesis Pathway interactions Physical activity Physicians Plasma Prevention RXR Recommendation Research Personnel Resolution Resources Retrospective Studies Risk Risk Factors Role Signal Transduction Somatomedins Specificity Specimen Structure of beta Cell of islet TNF gene Time Tumor Markers Tumor Necrosis Factor-alpha Variant Vitamin D Weight Women&apos s Health Work adiponectin base cancer epidemiology cancer prevention cancer risk carcinogenesis cohort comparative genomic hybridization cost design diet and cancer energy balance follow-up improved indexing inflammatory marker interest mortality prospective receptor response sedentary

项目摘要

DESCRIPTION (provided by applicant): Pancreatic cancer represents the fourth most common cause of cancer-related mortality. Nonetheless, relatively little is known about the pathogenesis and epidemiology of this malignancy. In a previous R01 grant (R01CA86102), we pooled the resources of three large prospective cohort studies, the Nurses' Health Study, the Health Professionals Follow-up Study, and the Physician's Health Study to examine the epidemiology and pathogenesis of pancreatic cancer. In response to a NIH Program Announcement, PA-05- 040, "Molecular Approaches to Diet and Pancreatic Cancer Prevention," we now propose to extend our findings and our collaborations by including the resources of two additional large prospective cohort studies with extensive banked dietary data and biospecimens, the Women's Health Study and the Women's Health Initiative. Pooling of cases from these five large ongoing prospective cohort studies with long-term follow-up will allow a rigorous examination of hypotheses focusing on mechanisms of pancreatic cancer pathogenesis. We propose to examine 3 inter-related pathogenic pathways for pancreatic carcinogenesis: 1) energy balance, insulin and insulin-like growth factor signaling, 2) inflammation, and 3) vitamin D-related pathways. With the combined resources of these five cohort studies, we will study relevant exposures utilizing (1) prospectively collected data on diet, body habitus, physical activity, analgesic use, and other exposures (2) nutrient and hormonal biomarkers, and (3) genetic factors relevant to the pathways of interest. These exposures, plasma biomarkers, and genetic factors will be examined in relation to pancreatic cancer incidence as well as specific molecular alterations in pancreatic cancer specimens. The prospective design of these analyses will allow a rigorous examination of these risk factors while minimizing the potential biases that are inherent in retrospective studies of pancreatic cancer. By better understanding underlying mechanisms, dose-response relations, inter-relations among factors acting in similar pathways, variation in response due to genetic susceptibility, and specificity in associations to specific tumor markers, we can identify recommendations aimed at reducing the incidence and mortality from this highly lethal malignancy.

描述（由申请人提供）：胰腺癌是癌症相关死亡率的第四大原因。尽管如此，对这种恶性肿瘤的发病机理和流行病学知之甚少。在以前的R01赠款（R01CA86102）中，我们汇集了三项大型前瞻性队列研究的资源，护士健康研究，卫生专业人员随访研究以及医师的健康研究，以研究胰腺癌的流行病学和发病机理。为了回应NIH计划公告，PA-05-040，“饮食和胰腺癌预防的分子方法”，我们现在建议通过包括两项其他大型前瞻性队列研究的资源与广泛的饮食数据和生物生物症，妇女健康研究以及妇女健康研究以及妇女的健康启动，以扩展我们的发现和协作。从这五个大型正在进行的前瞻性队列研究中进行长期随访的病例汇总，将允许对关注胰腺癌发病机理机制的假设进行严格的检查。我们建议检查3种相关的致病途径，以实现胰腺癌的发生：1）能量平衡，胰岛素和胰岛素样生长因子信号传导，2）炎症和3）维生素D相关途径。借助这五项队列研究的合并资源，我们将研究使用（1）有关饮食，身体习惯，身体活动，镇痛和其他暴露的前瞻性收集数据（2）营养和荷尔蒙生物标志物，以及（3）与感兴趣的途径相关的遗传因素。这些暴露，血浆生物标志物和遗传因素将与胰腺癌发生率以及胰腺癌标本的特定分子改变有关。这些分析的前瞻性设计将允许对这些危险因素进行严格的检查，同时最大程度地减少胰腺癌回顾性研究固有的潜在偏见。通过更好地理解潜在的机制，剂量反应关系，在相似途径中作用的因素之间的相互关系，由于遗传敏感性而导致的响应变化以及与特定肿瘤标记的关联的特异性，我们可以确定旨在降低这种凶猛恶性肿瘤的发病率和死亡率的建议。