Project 1: Childhood Leukemia International Consortium Studies

项目总结（见说明）：白血病是15岁以下儿童最常见的癌症。尽管多年的研究，儿童白血病（CL）的原因仍然难以捉摸。由于其良好的致癌性和毒性，父母吸烟和家庭农药暴露经常在CL中进行研究。虽然一些研究表明CL与父母吸烟或家庭农药暴露之间存在联系，但由于个体研究中样本量小可能导致结果不一致，因此无法得出明确的结论。为了克服个别研究样本量小的局限性，拟议的研究将汇集数据（N~8000例病例和18000例对照）来自儿童白血病国际联盟（CLIC）内10个国家的14项病例对照研究，以：1）进行描述性分析，以评估白血病亚型频率的地理差异; 2）评估母亲/父亲吸烟或家庭农药暴露与CL在不同时间段（产前，妊娠期间和产后）之间的关联，并按组织学，免疫表型分层。和细胞遗传学亚型; 3）通过组织学、免疫表型和细胞遗传学亚型，研究遗传变异对父母吸烟或家庭杀虫剂暴露与CL之间关联的影响;以及4）维护CLIC网站（http：clic.berkeley.edu），以促进CLIC成员与外部社区之间的沟通。基于访谈的父母吸烟和家庭杀虫剂暴露数据将在研究中标准化。将从14项研究中的8项确定遗传数据，这些研究集中于7种异生物质代谢（CYP 1A 1、GSTM 1、GSTTI、GSTP 1、NQ 01和EPHX 1）和药物转运蛋白基因（MDR）的12种多态性。此外，将对细胞遗传学数据的可用性和质量进行评估，以促进亚型分析。将使用两阶段数据合并方法来联合收割机合并研究间的数据，以解释研究特定协变量和研究间异质性。建议的分析将提高我们对父母吸烟和家庭农药暴露在儿童白血病病因中的作用的理解。这将对CL的预防具有重要意义。

PROJECT SUMMARY (See instructions): Leukemia is the most common cancer in children under 15 years of age. Despite years of research, the causes of childhood leukemia (CL) remain elusive. Due to their well-characterized carcinogenicity and toxicity, parental tobacco smoking and home pesticide exposures are frequently studied in CL. Though some studies have suggested a link between CL and parental tobacco smoking or home pesticides exposure, no definite conclusion can be reached due to inconsistent results likely resulted from problems associated with small sample size in individual studies. To overcome the limitations associated with the small sample size of individual studies, the proposed study will pool data (N~8000 cases and 18000 controls) from 14 case-control studies from 10 countries within the Childhood Leukemia International Consortium (CLIC) to: 1) conduct descriptive analyses to assess geographical differences in the frequency of leukemia subtypes; 2) assess the association between maternal/paternal smoking or home pesticide exposures and CL during different time periods (prenatal, during pregnancy, and postnatal) stratified by histologic, immunophenotypic. and cytogenetic subtypes; 3) examine the influence of genetic variation on the association between parental smoking or home pesticide exposures and CL by histologic, immunophenotypic and cytogenetic subtypes; and 4) maintain the CLIC website (http://clic.berkeley.edu) to facilitate communication among CLIC members and outside communities. Interview-based exposure data on parental smoking and home pesticides will be standardized across studies. Genetic data will be ascertained from 8 of the 14 studies focusing on 12 polymorphisms of seven xenobiotic metabolizing (CYP1A1, GSTM1, GSTTI, GSTPl, NQ01, and EPHX1) and drug transporter genes (MDR). In addition, availability and quality assessment of cytogenetic data will be conducted to facilitate subtype analyses. A two-stage data pooling method will be used to combine data across studies to account for study-specific covariates and inter-study heterogeneity. The proposed analyses will enhance our understanding of the roles of parental tobacco smoking and home pesticide exposure etiology of childhood leukemia. This will have important implications for prevention of CL.