Environmental and Molecular Epidemiology of Childhood Leukemia

项目摘要/摘要 这项拟议的研究建立在13年来治疗北加州儿童白血病的经验基础上 研究(NCCLS)，一项以人群为基础的病例对照研究，包括约40%的拉美裔美国人，这是一个传统的 未被充分代表的族群。拟议的研究将继续使用多学科和跨学科的 综合研究环境、分子、遗传、生物和流行病学因素的途径 儿童白血病，并改进化学品暴露评估。大约1,000名儿童白血病 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~1230例匹配 95%的受试者已经登记了DNA进行基因分型。调查 建议将研究环境和遗传风险因素如何相互作用，并探索 少见和研究不足的儿童白血病亚型，如急性髓系白血病和其他由分子定义的群体 和表观遗传标记。为了达到足够的统计能力，我们建议额外招收~660人 儿童白血病病例(约530例ALL；85例AML)和约660例匹配对照 加州38个研究县的儿科肿瘤学家的全面、快速报告网络。这个 由此产生的总样本量约为1,660例白血病病例(1,360例ALL，245例急性髓系白血病)和1,890例匹配对照 允许我们探索与出生前和产后住宅暴露于杀虫剂有关的假设，持续 有机污染物、苯暴露的来源以及ALL和AML的风险增加，以及这些 风险可能因白血病亚型而异，并受代谢基因变异的影响。我们还将检查 免疫功能对儿童ALL、B细胞ALL和普通ALL(c-ALL)发病风险的影响 亚型，以及参与免疫功能调节的基因如何改变这些关联。 我们将对大约10,000个基因变异进行大规模的基因分型，并使用一些最近开发的 分析复杂的多维遗传和流行病学数据的方法。

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.