Childhood Leukemia International Consortium (CLIC)

描述（由申请人提供）：儿童白血病是全球儿童的主要癌症，但与成人癌症相比，它是一种罕见的疾病。其病因在很大程度上仍然未知，主要是由于其生物多样性和多因素病因涉及遗传和环境因素之间的相互作用。考虑到基因与环境的相互作用，以往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。当考虑到白血病亚型，即急性淋巴细胞白血病与髓细胞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，这个问题进一步复杂化。为了克服单个研究的样本量限制，儿童白血病国际联盟（CLIC）最近成立，包括一个由11个研究小组组成的国际小组，目的是分享正在进行的儿童白血病病例对照和基于家庭的三人组研究的可比数据。CLIC的总体目标是实现更大的能力，特别是在亚型分析方面，复制新的发现，并通过大量的合作努力节省大量的成本。作为该联盟的第一个原理证明，该项目建议进行汇总分析，以评估在怀孕期间使用叶酸补充剂、母亲饮酒（已知会降低叶酸的生物利用度）和亚甲基四氢叶酸还原酶（MTHFR）遗传变异在儿童白血病的组织学和细胞遗传学亚型发展中的作用，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，结果是3300多例病例和4400例对照。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的异质性。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，促进联盟成员与更广泛的科学界之间的交流。国际癌症研究机构在建立财团方面有丰富的经验，与该机构的合作将为这项拟议的联合研究增加力量。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。为了克服研究样本量有限的局限性，特别是对于罕见的白血病亚型，儿童白血病国际联盟（CLIC）最近成立，包括11个国际研究团队，目的是分享正在进行的儿童白血病研究的可比数据。我们建议通过结合北加州、加拿大、英国、法国和澳大利亚六项儿童白血病病例对照研究的数据来评估母亲叶酸摄入量、母亲饮酒和叶酸代谢相关基因的作用，并评估这些因素之间的相互作用，这些研究包括3300多例病例和4400例对照。通过这项联合研究，我们计划阐明叶酸和特定基因的病因学作用，同时为该联盟在儿童白血病研究中的原理证明。

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.