Childhood Leukemia and Environmental Exposures

描述(由申请人提供)：这项建议旨在确定环境暴露和儿童白血病之间的病因学联系。该提案扩大了一项正在进行的针对0至14岁儿童的病例对照研究，该研究已在加利福尼亚州北部和中部的35个县成功实施。值得注意的是，受试者中有很高比例(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。这项拟议的研究将采用一种近似于基于人群确定的设计，扩大样本量(从400个新诊断的事件病例增加到1,148个新诊断的事件病例)，并改进在“儿童白血病与环境暴露”(1998年至2003年，R01 ES 09137)的头五年期间制定的设计和分析程序。每个病例的两名匹配的对照受试者将从全州出生登记中随机选择。提高人们对主要亚型(急性淋巴细胞白血病和急性髓系白血病)中白血病的分子和细胞遗传学多样性的认识，以及这种多样性对临床和流行病学研究的重要性，强调了揭示不同分子亚型白血病的病因的必要性。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联。在疾病分类方面，病例受试者的生物样本将包括预先处理的骨髓和外周血(在确诊时收集)和存档的新生儿血液样本(在出生时收集)。为了研究遗传易感性，口腔细胞标本将从病例、对照及其生母中收集。为了测量环境化学品暴露的微量营养素和生物标志物，将从7岁以下病例的亲生母亲及其匹配的对照组收集外周血液样本。将通过与亲生父母的详细面谈收集各种环境暴露的数据(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)。这些关于环境暴露和遗传特征的综合信息，加上按西班牙裔地位改进的疾病分类和分层，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.