Childhood Leukemia International Consortium (CLIC)

儿童白血病国际联盟 (CLIC)

基本信息

批准号：
7388573
负责人：
Patricia A Buffler
金额：
$ 6.24万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-27 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7388573
关键词：
2&apos -Deoxythymidine Abbreviations Accounting Acute Acute Lymphocytic Leukemia Acute Myelocytic Leukemia Address Adult Affect Age-Years Alcohol consumption Alcohols Australia B-Lymphocytes Beer Beverages Biodiversity Biological Availability Breast Feeding California Canada Case-Control Studies Child Childhood Leukemia Chromosomal translocation Collaborations Communication Communities Confidence Intervals Consumption Cost Savings Cytogenetics Data Data Set Deoxyuridine Development Environmental Health Environmental Risk Factor Epidemiology Etiology Family Folate France Genes Genetic Genotype Head and neck structure Heterogeneity Individual Institutes Intake International International Agency for Research on Cancer International Classification of Diseases Joints Lymphoid Malignant Neoplasms Malignant neoplasm of lung Meta-Analysis Methylenetetrahydrofolate reductase (NADPH)Modeling Modification Myeloid Leukemia National Cancer Institute Odds Ratio Persons Pregnancy Principal Investigator Rare Diseases Research Research Personnel Resources Risk Risk Factors Role Sample Size San Francisco Single Nucleotide Polymorphism Staging T-Cell Leukemia Time United Kingdom Universities Wine alcohol consumption during pregnancy base case control distilled alcoholic beverage experience folic acid metabolism gene environment interaction genetic variant leukemia member novel symposium

项目摘要

DESCRIPTION (provided by applicant): Childhood leukemia is the leading cancer in children worldwide, yet it is a rare disease compared to adult cancers. Its etiology remains largely unknown, mainly due to its biological diversity and the multifactorial etiology involving interactions between genetic and environmental factors. Previous studies often lacked adequate statistical power to investigate risk factors of childhood leukemia taking into account gene-environment interaction. This problem is further compounded when considering leukemia subtypes, i.e., acute lymphoid vs. myeloid leukemia and specific cytogenetic subtypes characterized by chromosome translocation(s). To overcome the sample size limitations of individual studies, the Childhood Leukemia International Consortium (CLIC) was recently established, including an international group of eleven research teams with the aim of sharing comparable data from ongoing case-control and family-based trio studies on childhood leukemia. The overall objectives of CLIC are to achieve greater power, especially for subtype analyses, replicate novel findings, and afford substantial cost savings through large collaborative efforts. As the first proof of principle for this consortium, this project proposes to conduct pooled analyses to evaluate the role of the use of folate supplements during pregnancy, maternal alcohol consumption (known to reduce folate bioavailability), and methylenetetrahydrofolate reductase (MTHFR) genetic variants in the development of childhood leukemia by histological and cytogenetic subtype, and to assess the interactions between these factors. To achieve these aims, we will combine data from six studies in Northern California, Canada, the United Kingdom, France, and Australia, resulting in over 3,300 cases and 4,400 controls. Data will be pooled centrally at the University of California, Berkeley and distributed to the investigators for specific analyses. Statistical analyses will take into consideration study heterogeneity using appropriate models. International collaborators will meet in person annually and will communicate by conference call to discuss the organization of the consortium and progress with data pooling and analyses. We also plan to establish a website that will publicize the activities of the consortium and facilitate communication between consortium members and the wider scientific community. Collaboration with the International Agency for Research on Cancer, which has extensive experience in establishing consortia, adds strength to this proposed joint research. Childhood leukemia is the leading cancer in children worldwide, yet it remains a rare disease. To overcome the limitation of studies with limited sample size, especially for rarer leukemia subtypes, the Childhood Leukemia International Consortium (CLIC) was recently established, including eleven international research teams, with the aim of sharing comparable data from ongoing studies on childhood leukemia. We propose to evaluate the role of maternal folate intake, maternal alcohol consumption, and genes involved in folate metabolism, and to assess the interactions between these factors by combining data from six case-control studies of childhood leukemia in Northern California, Canada, the United Kingdom, France, and Australia, resulting in over 3,300 cases and 4,400 controls. Through this joint research, we plan to elucidate the etiologic role of folate and specific genes, while establishing a proof of principle for the consortium in childhood leukemia research.

描述（由申请人提供）：儿童白血病是全世界儿童的主要癌症，但与成人癌症相比，它是一种罕见的疾病。其病因仍然很大程度上未知，主要是由于其生物多样性以及涉及遗传和环境因素之间相互作用的多因素病因。先前的研究往往缺乏足够的统计能力来调查儿童白血病的危险因素，同时考虑到基因与环境的相互作用。当考虑白血病亚型（即急性淋巴性白血病与髓性白血病）以及以染色体易位为特征的特定细胞遗传学亚型时，这个问题变得更加复杂。为了克服个别研究的样本量限制，儿童白血病国际联盟 (CLIC) 最近成立，其中包括一个由 11 个研究团队组成的国际小组，旨在共享正在进行的儿童病例对照和基于家庭的三人研究的可比较数据白血病。 CLIC 的总体目标是获得更大的能力，特别是在亚型分析方面，复制新颖的发现，并通过大规模协作努力节省大量成本。作为该联盟的第一个原则证明，该项目建议进行汇总分析，以评估怀孕期间使用叶酸补充剂、孕产妇饮酒（已知会降低叶酸生物利用度）以及亚甲基四氢叶酸还原酶 (MTHFR) 基因变异在妊娠期的作用。通过组织学和细胞遗传学亚型来研究儿童白血病的发展，并评估这些因素之间的相互作用。为了实现这些目标，我们将结合来自北加州、加拿大、英国、法国和澳大利亚的六项研究的数据，得出 3,300 多个病例和 4,400 多个对照。数据将集中在加州大学伯克利分校，并分发给研究人员进行具体分析。统计分析将使用适当的模型考虑研究异质性。国际合作者将每年亲自会面，并通过电话会议进行沟通，讨论联盟的组织以及数据汇集和分析的进展。我们还计划建立一个网站，宣传联盟的活动并促进联盟成员与更广泛的科学界之间的沟通。与国际癌症研究机构的合作在建立联盟方面拥有丰富的经验，为这项拟议的联合研究增添了力量。儿童白血病是全世界儿童的主要癌症，但它仍然是一种罕见的疾病。为了克服样本量有限的研究限制，特别是针对较罕见的白血病亚型，最近成立了儿童白血病国际联盟（CLIC），其中包括 11 个国际研究团队，旨在共享正在进行的儿童白血病研究的可比数据。我们建议评估母亲叶酸摄入量、母亲饮酒量和参与叶酸代谢的基因的作用，并通过结合来自北加州、加拿大、美国的六项儿童白血病病例对照研究的数据来评估这些因素之间的相互作用。英国、法国和澳大利亚，导致 3,300 多例病例和 4,400 例控制病例。通过这项联合研究，我们计划阐明叶酸和特定基因的病因作用，同时为该联盟在儿童白血病研究中建立原理证明。