Environmental and Molecular Epidemiology of Childhood Leukemia

儿童白血病的环境和分子流行病学

基本信息

批准号：
7944108
负责人：
Patricia A Buffler
金额：
$ 189.19万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-01-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7944108
关键词：
Abbreviations Acute Acute Lymphocytic Leukemia Acute Myelocytic Leukemia Address Advisory Committees Air Air Pollutants Archives Area Aromatic Polycyclic Hydrocarbons B-Cell Acute Lymphoblastic Leukemia Basic Science Benzene Biological Biology Blood Blood specimen Bone Marrow Calibration California Cancer Center Candidate Disease Gene Case-Control Studies Centers for Disease Control and Prevention (U.S.)Characteristics Charities Chemical Exposure Chemicals Child Childhood Childhood Acute Lymphocytic Leukemia Childhood Leukemia Chromosome abnormality Chromosomes Classification Common Acute Lymphoblastic Leukemia Confidence Intervals County Cytogenetics DNA DNA Databases DNA Repair Data Data Collection Data Set Diagnosis Diagnostic Diet Dust Enrollment Ensure Environment Environmental Exposure Environmental Risk Factor Epidemiologic Factors Epidemiology Ethnic group Etiology Exposure to Fluorescent in Situ Hybridization Foundations Funding Genes Genetic Genetic Predisposition to Disease Genetic Variation Genotype Geographic Information Systems Germ Lines HLA Antigens Haplotypes Health Services Hispanics Home environment Household Human Hypersensitivity Immune Immune Response Genes Immune response Immunity Infection Interdisciplinary Study International Interview Joints Laboratories Life Lymphoblastic Leukemia Lymphocyte Major Histocompatibility Complex Major Histocompatibility Complex Gene Malignant Childhood Neoplasm Malignant Neoplasms Mass Fragmentography Measurement Measures Metabolism Methylation Molecular Cytogenetics Molecular Epidemiology Molecular Genetics Mutation Natural History Newborn Infant Nomenclature Nonhomologous DNA End Joining Odds Ratio Oxidative Stress Parents Participant Particulate Matter Patient Self-Report Pesticides Polychlorinated Biphenyls Population Heterogeneity Population Study Public Health Questionnaires Recording of previous events Regulation Reporting Research Research Institute Research Personnel Risk Saliva Sample Size Sampling San Francisco Single Nucleotide Polymorphism Specimen Study Subject Superfund Surveys Susceptibility Gene System Testing Toxicology United States Environmental Protection Agency Universities Variant Xenobiotic Metabolism Xenobiotics air sampling case control environmental chemical environmental chemical exposure epidemiologic data folic acid metabolism gene environment interaction genetic risk factor genetic variant genome wide association study human AKAP13 protein immune function improved interdisciplinary approach leukemia peripheral blood pollutant population based programs prospective public health relevance response volatile organic compound

项目摘要

DESCRIPTION (provided by applicant): This is an amended application for the third competing renewal (years 11-15) of the Northern California Childhood Leukemia Study (NCCLS), a population-based, case-control study that currently has ~1,000 childhood leukemia cases and 1,300 matched controls, annotated with extensive environmental data and banked DNA. Approximately 40% of the study population is Hispanic. For this competitive renewal, the investigators propose to evaluate three hypotheses: 1) the risk of childhood ALL and the subtypes B-cell ALL and common ALL are associated with immune function in response to infection early in life, variants in immune function genes, and their joint effects; 2) risk of AML, ALL, and specific ALL subtypes are associated with self-reported pre- and post-natal residential exposure to environmental chemicals, variants in xenobiotic transport metabolism genes, and their joint effects; 3) risk of AML, ALL, and specific ALL subtypes are associated with calibrated levels of specific VOCs (volatile organic compounds), pesticides, and POPs (persistent organic pollutants), and these associations are modified by variants in xenobiotic transport metabolism genes. Five aims are proposed to test these hypotheses. The first aim is to collect demographic and environmental data and biologic specimens from ~660 new cases of childhood leukemia and 660 matched controls. Aim 2 is to collect home environmental dust and air samples in a stratified random sample of 300 new homes in order to calibrate interview data and household characteristics. Aim 3 is to collect germline genetic data from the existing and new subjects in order to genotype approximately 10K SNPs using a candidate gene approach. Aim 4 is to examine the main effects of genes and environmental exposures for risk of childhood leukemia subtypes, using existing and new data. Aim 5 is to examine gene-environment interactions within the dataset. For each sub-aim, differences in effect by Hispanic status will be assessed. PUBLIC HEALTH RELEVANCE: The multidisciplinary research team in the Northern California Childhood Leukemia Study (NCCLS) proposes to examine how environmental, immune, and genetic risk factors for childhood leukemia interact, and will explore the etiology of rare and understudied subtypes of leukemia. Detailed information on immunity and residential exposures to pesticides, persistent organic pollutants, and benzene will be available for approximately 1,660 leukemia cases and 1,890 matched controls, and biospecimens will be collected to conduct molecular and genetic susceptibility studies. The culturally diverse population of the NCCLS ensures that environmental and genetic exposures unique to Hispanics will be examined.

描述（由申请人提供）：这是北加州儿童白血病研究 (NCCLS) 第三次竞争更新（11-15 年）的修订申请，这是一项基于人群的病例对照研究，目前有约 1,000 名儿童白血病患者病例和 1,300 个匹配对照，并附有大量环境数据和储存的 DNA 注释。大约 40% 的研究人群是西班牙裔。对于这种竞争性更新，研究人员建议评估三个假设：1）儿童 ALL 以及 B 细胞 ALL 亚型和普通 ALL 的风险与生命早期感染的免疫功能、免疫功能基因的变异以及它们的共同作用； 2) AML、ALL 和特定 ALL 亚型的风险与自我报告的产前和产后居住环境化学品暴露、外源物质转运代谢基因变异及其联合效应相关； 3) AML、ALL和特定ALL亚型的风险与特定VOC（挥发性有机化合物）、杀虫剂和POP（持久性有机污染物）的校准水平相关，并且这些关联通过外源物质运输代谢基因的变异而改变。提出了五个目标来检验这些假设。第一个目标是从约 660 例儿童白血病新病例和 660 例匹配对照中收集人口和环境数据以及生物样本。目标 2 是在 300 个新住宅的分层随机样本中收集家庭环境灰尘和空气样本，以校准访谈数据和家庭特征。目标 3 是从现有和新受试者收集种系遗传数据，以便使用候选基因方法对大约 10K SNP 进行基因分型。目标 4 是利用现有数据和新数据检查基因和环境暴露对儿童白血病亚型风险的主要影响。目标 5 是检查数据集中的基因与环境的相互作用。对于每个子目标，将评估西班牙裔身份的影响差异。公共健康相关性：北加州儿童白血病研究 (NCCLS) 的多学科研究小组提议研究儿童白血病的环境、免疫和遗传风险因素如何相互作用，并将探索罕见和未被充分研究的白血病亚型的病因。将提供约 1,660 例白血病病例和 1,890 例匹配对照的免疫和住宅接触农药、持久性有机污染物和苯的详细信息，并将收集生物样本以进行分子和遗传易感性研究。 NCCLS 的文化多元化人群确保对西班牙裔独特的环境和遗传暴露进行检查。