Pilot Study of Childhood Leukemia in Guatemala

危地马拉儿童白血病试点研究

基本信息

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
项目类别：
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

项目摘要

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）：西班牙裔儿童的儿童白血病 (CL) 发病率是世界上最高的，尽管人们对这一观察结果背后的机制和决定因素知之甚少。人们普遍认为，CL 风险是通过个体遗传易感性与环境和内源性物质暴露之间的相互作用来调节的。拟议研究的长期目标是确定导致西班牙裔儿童 CL 发病率升高的特定遗传因素和环境暴露的组合。由于其多样化的西班牙裔人口主要由纯种土著和混血（混血）土著欧洲人组成，以及广泛使用生物质燃料用于取暖和烹饪，危地马拉提供了一个理想的模型系统，用于研究可疑致癌燃烧产物的暴露情况。患这种疾病的风险最高的种族人群。然而，在危地马拉进行此类研究之前，需要进行一项试点研究，以确定在这个很大程度上未被充分研究的人群中进行流行病学评估的可行性。这样的试点还将提供识别不可预见的障碍并随后修改协议以克服这些障碍的机会。因此，拟议试点研究的目的包括识别并招募来自危地马拉城一家三级儿科肿瘤医院的 50 名患有 CL 的儿童，以及 50 名年龄、性别、城市与农村状况相匹配的健康对照（被确定为心血管儿科的健康兄弟姐妹）。邻近三级心血管转诊中心的患者）。其他目标包括开发、验证和管理有效的调查工具，以记录 CL 的相关流行病学和环境暴露情况，并收集病例的诊断性骨髓和缓解期外周血以及病例、对照及其父母的唾液。这项试点研究的成功与否将通过受试者招募和生物样本收集的响应率、调查工具有效性子研究的结果以及病例和对照的可比性来衡量。如果成功，这项拟议的研究将推动对遗传因素进行全面的病例对照研究。危地马拉儿童白血病的环境流行病学。这样的研究将填补关于 CL 肿瘤生物学、与西班牙裔种族相关的遗传易感性以及与燃烧产物和风险的假定因果关系的已知空白。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知识的重要空白，包括观察到的西班牙裔儿童发病率上升以及暴露于环境燃烧产物的假定因果关系。为了确定在危地马拉（一个很大程度上未被充分研究的人群）进行全面的遗传和环境流行病学研究的可行性，我们建议进行初步试点研究。在该试点中，我们计划招募 50 名儿童白血病病例和 50 名匹配的健康对照，以获得有关相关环境和流行病学暴露的详细信息，并收集生物样本用于未来的分子和遗传学研究。该试点项目的成功将为未来的全面病例对照研究提供初步数据。