Pilot Study of Childhood Leukemia in Guatemala

危地马拉儿童白血病试点研究

• 批准号: 8358777
• 负责人: Libby Morimoto
• 金额: $ 24.54万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-08 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358777
• 关键词: Accounting; Acute; Acute Myelocytic Leukemia; Admixture; Adult; Affect; African; Age; American; Amerindian; Aromatic Polycyclic Hydrocarbons; Bathing; Biological Models; Biomass; Bone Marrow; California; Carcinogens; Cardiovascular system; Case-Control Studies; Child; Childhood; Childhood Leukemia; Cities; Clinical; Collaborations; Collection; Costa Rica; Country; Cytogenetics; DNA; Data; Developing Countries; Development; Diagnostic; Disease; Disease remission; Ecuador; Enrollment; Environmental Epidemiology; Environmental Exposure; Epidemiologic Studies; Epidemiology; Ethnic Origin; European; Exposure to; Feasibility Studies; Future; Garbage; Genetic; Genetic Predisposition to Disease; Genomics; Genotype; Goals; Guatemala; Hand; Heating; Hispanics; Home environment; Hospitals; Household; Human; Incidence; Indigenous; Individual; Inherited; International; Knowledge; Link; Malignant Neoplasms; Measures; Molecular Genetics; Parents; Participant; Patient Self-Report; Patients; Pediatric Oncology; Pilot Projects; Population; Pregnancy; Procedures; Process; Protocols documentation; Race; Recruitment Activity; Reporting; Research; Research Infrastructure; Resources; Risk; Risk Factors; Rural; Saliva; Siblings; Specimen; Surveys; Syndrome; Testing; Time; Tumor Biology; United States; Validation; Woman; Wood material; aged; base; case control; cigarette smoking; cooking; disorder risk; experience; genetic epidemiology; genome wide association study; high risk; particle; peripheral blood; postnatal; prenatal exposure; response; sex; success; volatile organic compound; wasting

DESCRIPTION (provided by applicant): Childhood leukemia (CL) rates among children with Hispanic ethnicity are among the highest in the world, although little is known about the mechanisms and determinants underlying this observation. CL risk is widely thought to be modulated by the interplay between individual genetic susceptibility and exposure to environmental and endogenous substances. The long-term goal of the proposed research is to identify combinations of specific genetic factors and environmental exposures that cause children with Hispanic ethnicity to have elevated rates of CL. With its diverse Hispanic population comprised primarily of pure indigenous and mixed (mestizo) indigenous-European peoples, as well as the widespread use of biomass fuels for heating and cooking, Guatemala presents an ideal model system to study exposure to suspected carcinogenic combustion products in an ethnic population most at risk for this disease. Before such a study could be undertaken in Guatemala, however, a pilot study is required to establish the feasibility of conducting an epidemiologic assessment in this largely understudied population. Such a pilot would also provide the opportunity to identify unforeseen barriers and subsequently modify the protocols to overcome such barriers. Therefore, the aims of the proposed pilot study include identifying and enrolling 50 children with incident CL from a tertiary pediatric oncology hospital in Guatemala City and 50 age, sex, and urban vs. rural status matched healthy controls (identified as healthy siblings of cardiovascular pediatric patients at an adjacent tertiary cardiovascular referral center). Additional aims include the development, validation, and administration of a valid survey instrument to record exposure to relevant epidemiologic and environmental exposures for CL, and to collect diagnostic bone marrow and remission peripheral blood on cases, and saliva on cases, controls, and their parents. Success for this pilot study will be measured by response rates for subject recruitment and biospecimen collection, results of a survey instrument validity sub-study, and comparability of cases and controls. If successful, this proposed study will motivate a full case-control study of the genetic and environmental epidemiology of childhood leukemia in Guatemala. Such a study would fill in gaps in what is known about the tumor biology of CL, of inherited genetic susceptibility associated with Hispanic ethnicity, and of putative causal relationships with products of combustion and risk. PUBLIC HEALTH RELEVANCE: A case-control study of childhood leukemia in Guatemala can fill important gaps in our knowledge about its epidemiology, including the observed elevation in rates among children of Hispanic ethnicity and the putative causal relationship of exposure to environmental products of combustion. To establish the feasibility of conducting a full epidemiologic study of the genetic and environmental epidemiology in Guatemala, a largely understudied population, we propose to conduct an initial pilot study. In this pilot, we plan to enroll 50 cases of childhood leukemia and 50 matched healthy controls, to obtain detailed information on relevant environmental and epidemiologic exposures, and to collect biospecimens for future molecular and genetic studies. The success of the pilot project will provide preliminary data to motivate a future full case-control study.

描述（由申请人提供）：西班牙裔种族儿童的儿童白血病（CL）率是世界上最高的，尽管对这一观察结果的机制和决定因素知之甚少。 CL风险被广泛认为是由个体遗传易感性与暴露于环境和内源性物质之间的相互作用来调节的。拟议研究的长期目标是确定特定遗传因素和环境暴露的组合，这些因素和环境暴露导致西班牙裔种族的儿童的CL率升高。其多样化的西班牙裔人口主要由纯净的土著和混合（混血）本土欧洲人民组成，以及危地马拉的广泛使用生物质燃料用于供暖和烹饪，为可疑的癌燃烧产品研究了一种理想的模型系统，以研究这种疾病的可疑燃烧产物。但是，在危地马拉进行此类研究之前，需要进行试点研究，以确定对这一大量研究的人群进行流行病学评估的可行性。这样的飞行员还将提供机会确定不可预见的障碍，然后修改克服此类障碍的协议。因此，拟议的试点研究的目的包括识别和注册危地马拉市第三级儿科肿瘤学医院的50名儿童，以及50岁的年龄，性别，性行为，以及城市与农村状态相匹配的健康对照（被确定为健康的邻近第二纪托型心脏心脏儿科患者的健康兄弟姐妹）。其他目的包括开发，验证和给药有效的调查工具，以记录CL的相关流行病学和环境暴露，并在病例上收集诊断性的骨髓和诊断性骨髓，并在病例，控制案件及其父母的情况下进行唾液。这项试验研究的成功将通过对受试者募集和生物循环收集的响应率，调查仪器有效性子研究结果以及病例和对照的可比性的结果来衡量。如果成功，这项拟议的研究将激发遗传的完整病例对照研究 危地马拉儿童白血病的环境流行病学。这项研究将填补有关CL肿瘤生物学，与西班牙裔种族相关的遗传遗传易感性以及与燃烧和风险产物的假定因果关系的差异。 公共卫生相关性：危地马拉儿童白血病的病例对照研究可以填补我们对其流行病学的了解的重要空白，包括在西班牙裔种族儿童中观察到的升高和燃烧环境产品暴露的假定因果关系的提升。为了建立对危地马拉遗传和环境流行病学进行全面流行病学研究的可行性，这是一个在很大程度上研究的人群，我们建议进行最初的试点研究。在此试验中，我们计划招募50例儿童白血病和50例匹配的健康对照，以获取有关相关环境和流行病学暴露的详细信息，并收集生物测量以进行未来的分子和遗传研究。试点项目的成功将提供初步数据，以激发未来的完整案例对照研究。