Subtyping Bladder Cancer: A Multi-omic, Exposure-informed, Genealogical Approach (MErGE)

膀胱癌分型：多组学、暴露信息、系谱方法 (MERGE)

• 批准号: 10200705
• 负责人: HEIDI Anne HANSON
• 金额: $ 14.94万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-06 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200705
• 关键词: Algorithms; Arsenic; Award; Behavior; Biomedical Engineering; Cancer Biology; Cancer Cluster; Cancer Research Project; Characteristics; Clinical; Complex; Consensus; Data; Demography; Dimensions; Disease; Early Diagnosis; Elderly; Environment; Environmental Epidemiology; Environmental Exposure; Environmental Risk Factor; Epidemiologist; Epidemiology; Epigenetic Process; Etiology; Exhibits; Exposure to; Familiarity; Family; Family member; Gene Expression Profile; Genealogy; Genes; Genetic; Genetic Risk; Genomics; Germ-Line Mutation; Goals; Grant; Health Services Research; Health behavior; Hematologic Neoplasms; Hereditary Malignant Neoplasm; Heterogeneity; High-Risk Cancer; Histology; Human Genetics; Individual; International; Knowledge; Lead; Life; Life Cycle Stages; Life course epidemiology; Link; Longevity; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of lung; Malignant neoplasm of prostate; Malignant neoplasm of urinary bladder; Medical; Mentors; Methodology; Methods; Methylation; Molecular; Multiomic Data; Operative Surgical Procedures; Organ; Outcome; Pathology; Patients; Pattern; Population; Population Database; Predisposition; Recording of previous events; Records; Renal carcinoma; Research; Research Personnel; Risk; SECTM1 gene; Sampling; Science; Screening for cancer; Skin Cancer; Smoking; Smoking Behavior; Sociology; Techniques; Technology; Testing; The Cancer Genome Atlas; Training; Translating; Tumor Subtype; Universities; Urologic Oncology; Utah; Variant; Work; base; cancer diagnosis; cancer epidemiology; cancer prevention; cancer risk; cancer subtypes; cancer type; career; clinical practice; clinically relevant; comparative; design; drinking water; early life exposure; environment related cancer; experience; family genetics; field study; genetic epidemiology; genetic pedigree; genetic signature; improved; innovation; lymphatic cancer; mid-career faculty; molecular subtypes; multidisciplinary; multiple omics; novel; population based; professor; survival outcome; survival prediction; tissue archive; treatment response; tumor; urologic; water quality

Project Summary/Abstract This is an application for a K07 award for Dr. Heidi Hanson, a tenure-line Assistant Professor of Surgery at the University of Utah. Dr. Hanson is establishing herself as a young investigator in genetic and environmental cancer epidemiology. Her training in sociology, demography, and life course epidemiology, experience with advance quantitative methodologies, and familiarity with the Utah Population Database perfectly poise her innovative work in this field of study. However, she is lacking the necessary training in: 1) cancer biology and pathology; 2) cutting-edge genetic epidemiology pedigree methods; 3) genomic and epigenetic tumor profiling; and 4) managing and implementing successful multidisciplinary team science. This training will allow Dr. Hanson to achieve her goal to launch an independent cancer research program focused on improving precision strategies of cancer screening and treatment methods through gene-environment scientific discoveries. Dr. Hanson has assembled a mentoring team comprising of a primary mentor, Dr. Nicola Camp, a genetic epidemiologist and nationally renowned investigator, and two co-mentors: Dr. Orly Alter, a Utah Science Technology and Research Initiative (USTAR) associate professor of bioengineering and human genetics, and Dr. Ken Smith, an internationally known expert in population-based analyses and genetic/family epidemiology. Dr. Hanson has six advisors and one contributor with expertise in urologic oncology, clinical outcomes in urologic malignancies and health services research, etiology of bladder cancer, epigenetic changes, high risk cancer studies, pathology, and environmental epidemiology. Bladder cancer (BCa) is a heterogeneous disease, with strong support for multiple subtypes, including a basal/squamous-like (BASQ) tumor subtype. However, there is a lack of consensus for the number and characteristics of additional subtypes. BCa risk may be driven by both genetic and environmental risk factors, with different etiologies yielding different subtypes of BCa. In terms of familial clustering, these different etiological factors may exhibit as different multi-cancer configurations across a spectrum of organs (tumor spectrum). Using dimension reduction techniques to perform an integrative multi-omic analysis of BCa expression and methylation combined with information on etiological factors associated with BCa risk can lead to the identification of subtypes of BCa that are epidemiologically and clinically relevant. Dr. Hanson will accomplish this through the following research specific aims: 1) Utilize dimension reduction techniques for integrative analysis of BCa multi-omics data; 2) Determine BCa dimensions associated with environmentally- driven BCa subtypes; 3) Identify BCa dimensions associated with genetically-driven BCa subtypes. This research will prepare Dr. Hanson to design and implement a novel R01 application to further investigate the multi-omic cancer profiles across a spectrum of organs and advance gene-environment research.

项目摘要/摘要 这是为Heidi Hanson博士颁发的K07奖的申请， 犹他大学的手术。汉森博士正在建立自己是遗传和 环境癌症流行病学。她在社会学，人口统计学和生活课程流行病学方面的培训， 具有预先定量方法学的经验，并且熟悉犹他州人口数据库 在这个研究领域中完美地融入了她的创新工作。但是，她缺乏必要的培训： 1）癌症生物学和病理； 2）尖端的遗传流行病学方法； 3）基因组和 表观遗传肿瘤分析； 4）管理和实施成功的多学科团队科学。这 培训将使汉森博士能够实现她的目标，以启动以独立的癌症研究计划为重点 关于通过基因环境改善癌症筛查和治疗方法的精确策略 科学发现。 Hanson博士组建了一个由主要导师Nicola博士组成的指导团队 CAMP是一名遗传流行病学家和全国知名的调查员，以及两个合伙人：Orly Alter博士， 犹他州科学技术与研究计划（USTAR）生物工程副教授 遗传学和肯·史密斯（Ken Smith）博士，基于人群的分析和遗传/家族的国际知名专家 流行病学。 Hanson博士有六位顾问和一名贡献者，具有泌尿科肿瘤学专业知识，临床 泌尿科恶性肿瘤和卫生服务研究的结果，膀胱癌病因，表观遗传学 变化，高风险癌症研究，病理学和环境流行病学。 膀胱癌（BCA）是一种异质疾病，对多种亚型的支持很大，包括 基底/鳞状（BASQ）肿瘤亚型。但是，对于该数字缺乏共识和 其他亚型的特征。 BCA风险可能由遗传和环境风险因素驱动， 具有不同的病因，产生了不同亚型的BCA。在家庭聚类方面，这些不同 病因因子可能表现为各种器官范围（肿瘤的多种癌症）构型 光谱）。使用缩小技术进行BCA的综合多态分析 表达和甲基化结合有关与BCA风险相关的病因因素的信息可以引导 鉴定在流行病学和临床上相关的BCA亚型。汉森·威尔博士 通过以下研究特定目的来实现这一目标：1）利用缩小尺寸技术 BCA多媒体数据的综合分析； 2）确定与环境相关的BCA维度 驱动的BCA亚型； 3）确定与遗传驱动的BCA亚型相关的BCA维度。这 研究将使汉森博士准备设计和实施新颖的R01应用程序，以进一步研究 跨器官范围和预先基因环境研究的多摩尼克癌谱。