Metabolomic signatures of inflammation and metabolic health in relation to colorectal cancer risk

与结直肠癌风险相关的炎症和代谢健康的代谢组学特征

• 批准号: 10699979
• 负责人: Alaina Bever
• 金额: $ 3.99万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2026-09-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10699979
• 关键词: Academic Medical Centers; Biological; Biological Markers; Biostatistical Methods; Body mass index; Branched-Chain Amino Acids; C-Peptide; C-reactive protein; Cancer Etiology; Cessation of life; Characteristics; Chronic Disease; Clinical; Clinical Nutrition; Colorectal Cancer; Consumption; Coupled; Dana-Farber Cancer Institute; Data; Development; Diet; Dietary Factors; Dietary Intervention; Dietary Practices; Dimensions; Doctor of Philosophy; Elasticity; Environment; Epidemiologic Methods; Epidemiologist; Epidemiology; FRAP1 gene; Follow-Up Studies; Food; Frequencies; General Hospitals; Genetic; Goals; Health; Health Professional; Health Sciences; Human; Incidence; Inflammation; Inflammatory; Insulin Resistance; Interleukin-6; Intervention; Knowledge; Link; Malignant Neoplasms; Massachusetts; Mediating; Mediation; Mediator; Medicine; Mentors; Mentorship; Metabolic; Metabolic Pathway; Methods; Modeling; Nurses' Health Study; Obesity; Oncologist; Oxidative Stress; Pathogenesis; Pathway interactions; Pattern; Physical activity; Physicians; Plasma; Population Sciences; Principal Component Analysis; Processed Meats; Proliferating; Prospective Studies; Public Health Schools; Questionnaires; Receptors, Tumor Necrosis Factor, Type II; Research; Research Personnel; Risk Factors; Role; Sampling; Signal Pathway; Statistical Methods; Students; TNF gene; TNFRSF1B gene; Testing; Training; Tumor Necrosis Factor Receptor; Tumor Promoters; Unhealthy Diet; Variant; Woman; adipokines; adiponectin; cancer epidemiology; career; clinical epidemiology; clinical training; cohort; colorectal cancer prevention; colorectal cancer risk; data integration; design; dietary; early onset colorectal cancer; energy balance; experience; gastrointestinal; high body mass index; lifestyle factors; lifestyle intervention; medical schools; meetings; member; men; metabolomics; mid-career faculty; modifiable risk; mortality; neoplastic; novel; novel marker; novel strategies; nutrition; physical inactivity; population health; pre-doctoral; professor; programs; risk prediction; screening; symposium; tumor; waist circumference

Project Summary/Abstract Colorectal cancer (CRC) is the third most common cancer in both men and women. The role of inflammation and metabolic disturbance in the pathogenesis of CRC is well-established. However, the biological mechanisms underlying these pathways and how they may mediate the diet-CRC link are poorly understood. In this application, we propose to derive metabolomic signatures that characterize inflammation and metabolic health in three large cohorts: the Nurses’ Health Study I and II and Health Professionals Follow-up Study. We will use reduced rank regression, a novel statistical method that combines the data-driven approach of principal components analysis with prior knowledge of intermediate factors, to identify patterns of metabolites describing maximal variation in biomarkers and lifestyle factors that characterize 1) inflammation (TNF receptor superfamily member 1B, interleukin 6, C-reactive protein, and adiponectin) and 2) metabolic health (body mass index, waist circumference, C-peptide, physical activity, and adiponectin). We will then use elastic net regression to select the most important metabolites contributing to the two factors derived using reduced rank regression and test the association between these metabolomic signatures and CRC risk, independently and as a mediator of processed meat consumption. The goal of this project is to elucidate the biological mechanisms relating inflammation and metabolic health to CRC and, in the long-term, to generate strategies to optimize dietary and lifestyle interventions for CRC prevention. Ms. Bever (PI) will conduct this research under the mentorship of Dr. Meir Stampfer, Professor of Epidemiology and Nutrition at Harvard T.H. Chan School of Public Health (HSPH); Dr. Mingyang Song, Assistant Professor of Clinical Epidemiology and Nutrition at HSPH; Dr. Jeffrey Meyerhardt, a practicing gastrointestinal oncologist and researcher at the Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School (HMS); Dr. Liming Liang, Associate Professor of Statistical Genetics at HSPH; Dr. Edward Giovannucci, Professor of Epidemiology and Nutrition at HSPH; Dr. Andrew Chan, a practicing gastrointestinal oncologist and Director of Cancer Epidemiology at Massachusetts General Hospital; and Dr. Wei Zheng, Professor of Medicine and Associate Director for Population Sciences Research at Vanderbilt University Medical Center. Ms. Bever is a rising fourth-year student in the Harvard/MIT MD-PhD Program, about to begin her second year of the Population Health Sciences PhD program at HSPH. Her training plan includes coursework in advanced biostatistics and epidemiologic methods, local seminars and national conferences, and weekly meetings with mentors. The training plan has been designed to support Ms. Bever’s long-term goal of becoming a physician-epidemiologist with expertise in risk factors for cancer. The plan includes integration of clinical activities during Ms. Bever’s pre-doctoral training and continued opportunities for research during her last two years of medical school.

项目摘要/摘要 结直肠癌（CRC）是男性和女性中第三大常见的癌症。炎症的作用 CRC发病机理中的代谢灾难已经建立了良好的。但是，生物学 这些途径及其如何介导Diet-CRC连接的机制知之甚少。 在此应用中，我们建议得出表征注射和代谢的代谢组学特征 三个大型队列的健康：护士健康研究I和II和卫生专业人员随访研究。我们 将使用降低的等级回归，这是一种新颖的统计方法，结合了数据驱动的方法 主要成分分析具有中间因素的先验知识，以识别代谢物的模式 描述特征的生物标志物和生活方式因素的最大变化1）炎症（TNF受体 超家族成员1B，白介素6，C反应蛋白和脂联素）和2）代谢健康（体重 索引，腰围，C肽，身体活动和脂联素）。然后，我们将使用弹性网 回归以选择最重要的代谢产物，这些代谢产生了使用降低等级得出的两个因素 独立的回归和测试这些代谢组学特征与CRC风险之间的关联 作为加工肉类食用的调解人。该项目的目的是阐明生物学 与CRC有关注射和代谢健康的机制，从长远来看，制定策略 优化预防CRC的饮食和生活方式干预措施。 Bever女士（PI）将在 哈佛T.H.流行病学与营养学教授Meir Stampfer博士的精神职位陈学校 公共卫生（HSPH）； Mingyang Dr. Song，临床流行病学和营养助理教授 HSPH; Dana-Farber的实用胃肠道肿瘤学家兼研究人员Jeffrey Meyerhardt博士 哈佛医学院（HMS）癌症研究所兼医学教授； Liang博士，同事 HSPH统计遗传学教授； Edward Giovannucci博士，流行病学和营养教授 HSPH;实用的胃肠道肿瘤学家，癌症流行病学主任安德鲁·陈（Andrew Chan）博士 马萨诸塞州综合医院；以及Zheng博士，医学教授兼副主任 范德比尔特大学医学中心的人口科学研究。贝弗女士是一个上升的四年级 哈佛/麻省理工学院MD-PHD计划的学生即将开始她的人口健康第二年 HSPH的Sciences博士计划。她的培训计划包括高级生物统计学课程和 流行病学方法，当地的半身和民族会议以及每周与导师会议。 培训计划旨在支持Bever女士成为一名物理学家的长期目标 具有癌症危险因素的专业知识。该计划包括贝弗女士期间的临床活动的整合 博士前培训和在医学院的最后两年中继续进行研究的机会。