Admixture analysis of acute lymphoblastic leukemia in African American children: the ADMIRAL Study

非裔美国儿童急性淋巴细胞白血病的混合分析：ADMIRAL 研究

• 批准号: 10626271
• 负责人: Joseph Lubega
• 金额: $ 19.76万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10626271
• 关键词: Acute Lymphocytic Leukemia; Administrative Supplement; Admixture; Africa; African; African American; African ancestry; American; Biological; Biology; Cancer Control; Cell Lineage; Child; Childhood; Childhood Acute Lymphocytic Leukemia; Childhood Leukemia; Chromosome abnormality; Cities; Clinical; Clinical Data; Clinical Research; Collection; Complement; Cytogenetics; DNA; Data Set; Enrollment; Environment; Epidemiology; European; Fluorescent in Situ Hybridization; Gene Frequency; Genetic; Genomics; Genotype; Goals; Health Disparities Research; High Prevalence; Immune; Inherited; Institutional Review Boards; Literature; Low Prevalence; Malignant Childhood Neoplasm; Malignant Neoplasms; Molecular Epidemiology; Newly Diagnosed; Outcome; Parents; Pathologic; Pattern; Pediatric Hospitals; Phenotype; Plasma; Population; Prevalence; Prognosis; Prognostic Factor; Protocols documentation; Redwood; Relative Risks; Reporting; Research; Research Project Grants; Risk; Risk Factors; Single Nucleotide Polymorphism; T-Lymphocyte; Testing; Texas; Tissues; Uganda; Viral Load result; Virus; Virus Diseases; World Health Organization; admixture mapping; cancer health disparity; clinical phenotype; cohort; disparity elimination; early childhood; epidemiology study; genomic locus; high risk; improved; innovation; interest; leukemia; parent project; prognostic significance; programs; prospective; recruit; response; survival disparity; tumor; virome

Abstract This application is being submitted in response to the Notice of Special Interest (NOSI) identified as “NOT-CA- 22-057”. In our parent project titled “Admixture analysis of acute lymphoblastic leukemia (ALL) in African American children (ADMIRAL Study; R01CA239701), we are performing admixture mapping to identify ancestral genomic loci that may account for differential risk and unfavorable clinical phenotypes of ALL in African American (AA) children. In this Administrative Supplement Opportunity to Stimulate or Strengthen Global Cancer Health Disparities Research, we propose synergistic molecular epidemiology research to identify leukemia biology factors that potentially underly the same clinical problem (unfavorable ALL phenotypes) among children in Africa. The high burden of childhood ALL and urgent importance to effectively control the cancer in Africa is highlighted by the World Health Organization’s Global Initiative for Childhood Cancer. The goal of the proposed supplemental research project is to leverage this African childhood ALL cohort as a triangulating comparator that shares genetic ancestry with AA but lacks European admixture and has a distinctively different landscape of environmental immune challenges, namely, endemic viral infections. The purpose is to identify the biological underpinnings of unfavorable ALL prognostic factors in AA and African children that can be targeted to reduce ALL survival disparities in these populations. Our overarching approach is to characterize somatic, inherited, and environmental determinants of clinical differences in childhood ALL among world populations; the Specific Aims are to: 1. Identify the cytogenetic abnormalities that may underpin unfavorable ALL clinical phenotypes among children of African ancestry and their association with African/European genetic admixture. 2. Compare the prevalence of replicated inherited single nucleotide variants (SNVs) that are reported in the literature to be associated with ALL risk and outcomes among African, AA and EA children. 3. Characterize the plasma exogenous virome in children with ALL in Africa.

抽象的 该申请是根据特殊利益通知（NOSI）提交的 22-057“。 美国儿童（海军上将研究； R01CA239701），我们正在执行混合映射以识别祖先 可能解释非裔美国人所有人的差异风险和不利的临床表型的基因组基因局 （aa）孩子。在这种行政补充的机会中，可以刺激或增强全球癌症健康 差异研究，我们提出协同分子流行病学研究以识别白血病生物学 非洲儿童中可能在同一临床问题（不利的所有表型）下可能存在的因素。 强调了童年时代的高度燃烧和有效控制非洲癌症的迫切重要性 由世界卫生组织的全球儿童癌症倡议。提议的目标 补充研究项目是要利用这个非洲童年的同类，作为一个三角比较器， 与AA共享遗传血统，但缺乏欧洲混合物，并且具有明显不同的景观 环境免疫挑战，即内在病毒感染。目的是识别生物学 AA和非洲儿童的所有预后因素不利的基础 这些人群中的所有生存分布。我们的总体方法是表征躯体，遗传和 世界人口中童年临床差异的环境决定者；具体目标 为：1。确定可能支持所有临床表型的细胞遗传学异常 非洲血统的孩子及其与非洲/欧洲遗传混合物的联系。 2。比较 文献中报告的复制遗传单核苷酸变体（SNV）的流行率是 与非洲，AA和EA儿童之间的所有风险和结果有关。 3。表征血浆 非洲所有儿童的外源性病毒蛋白。