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研究者提供研究经验和职业发展机会，其职业抱负是增进对流行病学和血液相关癌症预防的理解。该研究的重点是多发性骨髓瘤（MM），其病因尚不清楚。 MM 患者的 5 年生存率较低 (30%)，这凸显了确定可改变的危险因素的紧迫性。最近有报道称肥胖可以预测 MM，因此能量平衡的其他相关因素（例如成人体重增加和/或体力活动）也可能与 MM 相关。此外，胰岛素样生长因子 (IGF)-1 通路的失调可能预测 MM 风险。我们建议在一项巢式匹配病例对照研究中评估这些假设，使用来自三项大型前瞻性队列研究的综合问卷和生物标志物数据：护士健康研究、健康专业人员随访研究和妇女健康研究。我们预计合并样本量为 380 例病例和 760 名对照，其中 100 例病例和 200 名对照将拥有存档的血浆和 DMA 用于生物标志物分析。我们将进行条件逻辑回归分析，以评估肥胖、成人体重增加、体力活动以及 IGF-1、IGF 结合蛋白 3、酸不稳定亚基和 C 肽的诊断前血浆水平与 MM 的关联。我们还将检查 5 个 IGF 相关基因的独特单倍型与 MM 的关联。这些分析将提供有关这些危险因素（肥胖除外）与 MM 关系的第一批数据。该项目利用了钱宁实验室、丹娜法伯/哈佛癌症中心及其多发性骨髓瘤孢子以及哈佛公共卫生学院的丰富环境来提供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；共同发起人博士的有意指导计划。 Graham Colditz 和 Kenneth Anderson，他们每个人都提供了宝贵的经验和专业知识；参加当地工作组和系列研讨会；以及出席专业会议。因此，拟议的项目代表了一个战略性的创新研究项目，旨在促进候选人的职业发展。