Childhood Leukemia and Environmental Exposures

描述（由申请人提供）：本提案旨在确定环境暴露与儿童白血病之间的病因学关联。该提案扩大了一项正在进行的0至14岁儿童病例对照研究，该研究已在加州北部和中部35个县成功实施。值得注意的是，很高比例的研究对象（约40%）是西班牙裔儿童，这在儿童白血病研究中是独一无二的。采用近似基于人群的确定设计，拟议的研究将扩大样本量（从400例到1148例新诊断病例），并改进“儿童白血病和环境暴露”（R01 ES 09137, 1998-2003）前五年开发的设计和分析程序。每个病例将从全州出生登记处随机选择两名匹配的对照受试者。随着人们对白血病主要亚型（急性淋巴细胞白血病和急性髓细胞白血病）的分子和细胞遗传学多样性的认识的提高，以及这种多样性对临床和流行病学研究的重要性，强调了揭示白血病分子不同亚群病因的必要性。我们将使用分子生物学技术来区分白血病亚群，并确定环境暴露与每个分子亚群的关系。对于疾病分类，病例受试者的生物标本将包括预处理骨髓和外周血（在诊断时采集）和存档的新生儿血液标本（在出生时采集）。为了研究遗传易感性，将从病例、对照和其生母中收集口腔细胞标本。为了测量微量营养素和环境化学物质暴露的生物标志物，将从7岁以下病例的亲生母亲及其匹配对照中收集外周血标本。将通过与亲生父母的详细面对面访谈收集广泛的环境暴露数据（包括父母的职业暴露、父母的烟草烟雾、杀虫剂和其他化学品、母婴饮食和儿童免疫因素）。这一关于环境暴露和遗传特征的综合信息，结合改进的疾病分类和西班牙裔身份分层，将为儿童白血病的病因学提供重要的见解。

DESCRIPTION (provided by applicant): This proposal is designed to identify etiologic associations between environmental exposures and childhood leukemia. The proposal expands an ongoing case control study of children ages 0 to 14 years that has been successfully implemented in 35 Northern and Central California counties. Notably, a high percentage of the subjects (about 40%) are children of Hispanic origin, which is unique in a study of childhood leukemia. Using a design that approximates population based ascertainment, the proposed study will expand the sample size (from 400 to 1148 newly diagnosed incident cases) and refine design and analytical procedures developed during the first five years of "Childhood Leukemia and Environmental Exposures" (R01 ES 09137, 1998-2003). Two matched control subjects for each case will be randomly selected from the statewide birth registry. Increased awareness of the molecular and cytogenetic diversity of leukemia within major subtypes (acute lymphoblastic leukemia and acute myeloid leukemia), and the significance of this diversity for clinical and epidemiologic research, underscore the need to uncover the etiologies of molecularly distinct subgroups of leukemia. We will use molecular-biologic techniques to differentiate leukemia subgroups and to identify the association of environment exposures with each molecular subgroup. For disease classification, biological specimens from case subjects will include pretreatment bone marrow and peripheral blood (collected at the time of diagnosis) and archived newborn blood specimens (collected at birth). To study genetic susceptibility, buccal cell specimens will be collected from cases, controls, and their biological mothers. To measure micronutrients and biomarkers of environmental chemical exposures, peripheral blood specimens will be collected from biological mothers of cases under age 7 and their matched controls. Data on a wide spectrum of environmental exposures (including parental occupational exposures, parental tobacco smoke, pesticides and other chemicals, maternal and child diet, and child immunological factors) will be collected through a detailed in-person interview with a biological parent. This comprehensive information on environmental exposures and genetic characteristics, in conjunction with improved disease classification and stratification by Hispanic status, will provide significant insights into the etiology of childhood leukemia.