Environmental and Molecular Epidemiology of Childhood Leukemia

项目总结/摘要 这项研究建立在北方加州儿童白血病13年的经验基础上 研究（NCCLS），一项基于人群的病例对照研究，其中包括约40%的西班牙裔，传统的 代表性不足的民族。拟议的研究将继续使用多学科和跨学科的方法， 综合研究环境、分子、遗传、生物和流行病学因素的方法， 儿童白血病，并改善化学品暴露评估。约1,000例儿童白血病 例[830例急性淋巴细胞白血病（ALL）和160例急性髓细胞白血病（AML）]和约1，230例匹配 已招募对照组，约95%的受试者可获得用于基因分型的DNA。调查 建议将研究环境和遗传风险因素如何为ALL的相互作用，并探讨病因， 罕见和研究不足的儿童白血病亚型，如AML和其他由分子生物学定义的组 和表观遗传标记。为了达到足够的统计功效，我们建议再招募约660名 儿童白血病病例（~530例ALL; 85例AML）和~660例匹配对照，使用已建立的 加州38个研究县的儿科肿瘤学家的全面、快速报告网络。的 总样本量约为1，660例白血病病例（1，360例ALL，245例AML）和1，890例匹配对照， 使我们能够探索与产前和产后住宅暴露于农药，持久性 有机污染物，苯暴露的来源和急性淋巴细胞白血病和急性粒细胞白血病的风险增加，以及这些 风险可能因白血病亚型而异，并因代谢基因的变异而改变。我们亦会研究 免疫功能对儿童ALL总体、B细胞ALL和普通ALL（c-ALL）风险的影响 亚型，以及这些关联如何被参与免疫功能调节的基因修饰。 我们将对约10，000种基因变异进行大规模基因分型，并采用一些最近开发的 复杂的多维遗传学和流行病学数据的分析方法。

PROJECT SUMMARY/ABSTRACT The proposed research builds on 13 years of experience with the Northern California Childhood Leukemia Study (NCCLS), a population-based case-control study which includes ~40% of Hispanics, a traditionally under-represented ethnic group. The proposed study will continue to use a multi- and transdisciplinary approach to comprehensively study environmental, molecular, genetic, biologic and epidemiologic factors of childhood leukemia, and to improve chemical exposure assessment. Approximately 1,000 childhood leukemia cases [830 acute lymphocytic leukemia (ALL) and 160 acute myelocytic leukemia (AML)] and ~1,230 matched controls have been enrolled with DNA for genotyping available in ~95% of subjects. The investigations proposed will examine how environmental and genetic risk factors for ALL interact, and explore the etiology of rare and understudied subtypes of childhood leukemia such as AML and other groups defined by molecular and epigenetic markers. To achieve adequate statistical power, we propose to enroll an additional ~660 childhood leukemia cases (~530 ALL; 85 AML) and ~660 matched controls using an established comprehensive, rapid reporting network of pediatric oncologists in the 38 California study counties. The resulting total sample size of ~1,660 leukemia cases (1,360 ALL, 245 AML) and 1,890 matched controls will allow us to explore hypotheses related to pre- and post-natal residential exposures to pesticides, persistent organic pollutants, and sources of benzene exposure and increased risks of ALL and AML, and how these risks may vary by leukemia subtype and be modified by variants in metabolizing genes. We will also examine the influence of immune function on the risk of childhood ALL overall, B-cell ALL and common-ALL (c-ALL) subtypes, and how these associations are modified by genes involved in the regulation of immune function. We will conduct large scale genotyping of ~10,000 gene variants, and employ a number of recently developed approaches for analysis of complex multidimensional genetic and epidemiologic data.