Energy Balance, IGF Dysregulation and Multiple Myeloma

能量平衡、IGF 失调和多发性骨髓瘤

• 批准号: 7921309
• 负责人: BRENDA M BIRMANN
• 金额: $ 9.54万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7921309
• 关键词: Acids; Address; Adult; American Cancer Society; Archives; Award; Biological Markers; Blood; Body mass index; C-Peptide; Cancer Center; Cell Line; Cells; Cessation of life; Cohort Studies; DNA; Data; Data Analyses; Diagnosis; Disease; Environment; Epidemiology; Etiology; Follow-Up Studies; Genes; Genetic; Haplotypes; Health Professional; Hematopoietic Neoplasms; Incidence; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth-Factor-Binding Proteins; Insulin-Like-Growth Factor I Receptor; Laboratories; Laboratory Study; Logistic Regressions; Malignant Neoplasms; Matched Case-Control Study; Mentors; Monoclonal gammopathy of uncertain significance; Multiple Myeloma; Nurses' Health Study; Obesity; Pathway interactions; Patients; Persons; Physical activity; Plasma; Prevention; Public Health Schools; Questionnaires; Regression Analysis; Reporting; Reproduction spores; Research; Research Personnel; Research Project Grants; Risk; Risk Factors; Sample Size; Sampling; Series; Serological; Single Nucleotide Polymorphism; Somatomedins; Specimen; Training Programs; United States; Up-Regulation; Weight Gain; Women' s Health; career; career development; case control; cohort; design; energy balance; experience; high risk; in vitro activity; innovation; meetings; migration; modifiable risk; mortality; mouse model; nutritional epidemiology; population based; prospective; research study; skills; working group

DESCRIPTION (provided by applicant): This Research Career Award application is intended to provide research experience and career development opportunities to a new investigator whose career aspiration is to advance the understanding of the epidemiology and prevention of blood-related cancers. The research focuses on multiple myeloma (MM), the etiology of which is poorly understood. The low (30%) 5-year survival of MM patients underscores the urgency of identifying modifiable risk factors. Obesity was recently reported to predict MM, and thus other correlates of energy balance such as adult weight gain and/or physical activity may also be related to MM. In addition, dysregulation of the insulin-like growth factor (IGF)-1 pathway may predict MM risk. We propose to evaluate these hypotheses in a nested matched case-control study, using combined questionnaire and biomarker data from three large prospective cohort studies: the Nurses' Health Study, the Health Professionals' Follow-up Study, and the Women's Health Study. We project a pooled sample size of 380 cases and 760 controls, of whom 100 cases and 200 controls will have archived plasma and DMA for the biomarker analyses. We will conduct conditional logistic regression analysis to estimate the association of obesity, adult weight gain, physical activity, and prediagnostic plasma levels of IGF-1, IGF binding protein 3, acid-labile subunit and C-peptide with MM. We will also examine the association of unique haplotypes of 5 IGF-related genes with MM. These analyses will contribute the first data on the relations of these risk factors (other than obesity) with MM. The project takes advantage of the rich environment of the Channing Laboratory, the Dana-Farber/Harvard Cancer Center and its Multiple Myeloma SPORE, and the Harvard School of Public Health for both research and career development support. The training program includes coursework to strengthen skills in genetic data analysis and nutritional epidemiology; a plan for intentional mentoring by the Co-Sponsors, Drs. Graham Colditz and Kenneth Anderson, each of whom offer valuable experience and expertise; participation in local working groups and seminar series; and attendance at professional meetings. Thus, the proposed project represents an innovative research project strategically designed to enhance the career development of the Candidate.

描述（由申请人提供）：本研究职业奖申请旨在为新的研究者提供研究经验和职业发展机会，其职业愿望是提高对流行病学和预防与血液相关的癌症的理解。该研究的重点是多发性骨髓瘤（MM），其病因对此的理解很少。 MM患者的低（30％）5年生存率强调了识别可修改风险因素的紧迫性。最近据报道肥胖可以预测MM，因此能量平衡的其他相关性（例如成人体重增加和/或体育活动）也可能与MM有关。此外，胰岛素样生长因子（IGF）-1途径的失调可能预测MM风险。我们建议在一项嵌套匹配的病例对照研究中评估这些假设，并使用三项大型前瞻性队列研究的合并问卷和生物标志物数据：护士健康研究，卫生专业人员的后续研究以及妇女健康研究。我们投影的样本量为380例和760个对照，其中100例和200例对照将对生物标志物分析进行存档等离子体和DMA。我们将进行有条件的逻辑回归分析，以估算IGF-1，IGF结合蛋白3，酸性亚基亚基和C肽与MM的肥胖，成人体重增加，身体活动和诊断性血浆水平的关联。我们还将研究5个IGF相关基因与MM的独特单倍型的关联。这些分析将贡献有关这些风险因素（肥胖症除外）与MM的关系的第一个数据。该项目利用了Channing实验室，Dana-Farber/Harvard Cancer Center及其多发性骨髓瘤的丰富环境以及哈佛公共卫生学院的研究和职业发展支持。培训计划包括加强遗传数据分析和营养流行病学技能的课程；共同发起人有意指导的计划，博士。 Graham Colditz和Kenneth Anderson，每个人都提供宝贵的经验和专业知识；参加本地工作组和研讨会系列；并参加专业会议。因此，拟议的项目代表了一个创新的研究项目，旨在增强候选人的职业发展。