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：
7579332
负责人：
CHARLES S FUCHS
金额：
$ 92.86万
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 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7579332
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 Follow-Up Studies Functional disorder Future GC gene Gene Cluster Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Variation Grant Haplotypes Health Health Professional Helicobacter pylori Hormonal Hormones Hybridization Array 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 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 Tumor Necrosis Factors VDR gene Variant Vitamin D Weight Women&apos s Health Work adiponectin base cancer epidemiology cancer prevention cancer risk carcinogenesis cohort comparative genomic hybridization cost design energy balance follow-up human TNF protein improved indexing interest mortality prospective response sedentary tumor

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的第四大常见原因。尽管如此，人们对这种恶性肿瘤的发病机制和流行病学知之甚少。在之前的 R01 资助 (R01CA86102) 中，我们汇集了三项大型前瞻性队列研究（护士健康研究、健康专业人员随访研究和医生健康研究）的资源，以研究胰腺癌的流行病学和发病机制。为了响应 NIH 计划公告 PA-05-040“饮食和胰腺癌预防的分子方法”，我们现在建议通过纳入另外两项大型前瞻性队列研究的资源来扩展我们的研究结果和合作，这些研究涉及广泛的库存膳食数据和生物样本、妇女健康研究和妇女健康倡议。将这五项正在进行的大型前瞻性队列研究中的病例进行汇总并进行长期随访，将能够对侧重于胰腺癌发病机制的假设进行严格的检验。我们建议检查胰腺癌发生的 3 种相互关联的致病途径：1) 能量平衡、胰岛素和胰岛素样生长因子信号传导，2) 炎症，以及 3) 维生素 D 相关途径。结合这五项队列研究的资源，我们将利用 (1) 前瞻性收集的有关饮食、身体习惯、体力活动、镇痛药使用和其他暴露的数据 (2) 营养和激素生物标志物，以及 (3) 遗传来研究相关暴露。与感兴趣的途径相关的因素。将检查这些暴露、血浆生物标志物和遗传因素与胰腺癌发病率以及胰腺癌样本中特定分子变化的关系。这些分析的前瞻性设计将允许对这些危险因素进行严格检查，同时最大限度地减少胰腺癌回顾性研究中固有的潜在偏差。通过更好地了解潜在机制、剂量反应关系、作用于相似途径的因素之间的相互关系、遗传易感性引起的反应变化以及与特定肿瘤标志物相关的特异性，我们可以确定旨在降低发病率和死亡率的建议这种高度致命的恶性肿瘤。