MOLECULAR EPIDEMIOLOGY OF CHILDHOOD LEUKEMIA

尽管儿童白血病患者的生存率有所提高， 儿童白血病的病因仍然不明。 目前的证据表明 遗传损伤破坏了淋巴细胞的正常分化过程， 和骨髓祖细胞。 遗传损伤可能是遗传的， 在子宫内，或可能发生在出生后。 暴露于环境致癌物 在这些间隔中的任何一个被怀疑引起有害的遗传 变化 本病例对照研究的目的是探讨 环境暴露和儿童白血病风险之间的关系， 利用分子生物学技术来表征 基因变化，以及考虑可能的效果修饰剂。 的 还将在病例和对照组中确定遗传变化的时间 使用从出生和口腔细胞获得的存档新生儿血液样品， 在面试。 对于病例组，[特定分子的患病率 将从几种标本类型（存档新生儿）中获得变化 血液、外周血、外周血和骨髓 诊断，和口腔细胞DNA在采访时），以确定 基因变化的时间。 这些变化将按以下因素分层： 父母自我报告的暴露情况，以确定儿童的遗传变化 与父母在出生前或出生期间自我报告的暴露相关 怀孕 这将证明暴露是否与遗传相关， 变化和这些变化发生的时间性质。 所有新诊断的儿童白血病病例（0-14岁）， 在大旧金山弗朗西斯科湾区的四家转诊医院之一 1995年至1998年期间的合格人数（n=2000人）。 两个匹配的对照组 将获得每个案件;朋友控制和出生证明 对照 朋友控制将从提供的提名者中随机选择 由父母在年龄、性别、居住国等方面与案件相匹配， 诊断和母亲的种族。 出生证明控制将是 从加州出生的婴儿中选择，这些婴儿在年龄，性别， 性别、出生县和种族。 两份问卷将 提供;父母自我管理的访谈，记录饮食， 怀孕前三个月的职业和居住记录 在怀孕期间，直到诊断出指示病例。 面对面 然后将安排访谈，以审查数据并收集更多 信息. 面试将以英语和西班牙语进行。 这项研究提供了特殊的设计优势，比早期的研究，由于 使用两个对照组和两种语言的面对面访谈，以及 基本上是一个以人口为基础的案件确定湾区。 然而，与其他研究最重要的区别是， 基因变化的时间方面与暴露，将导致 在儿童白血病病因学方面取得了重大进展。

Despite advances in the survival of patients with childhood leukemia, the causes of childhood leukemia remain unknown. Current evidence suggests that genetic damage disrupts the normal differentiation process of lymphoid and myeloid progenitor cells. Genetic damage may be inherited, may occur in utero, or may occur after birth. Exposure to environmental carcinogens during any of these intervals is suspected to cause detrimental genetic change. The objective of this case control study is to investigate the relationship between environmental exposures and the risk of childhood leukemia, utilizing molecular biology techniques to characterize the presence of genetic changes, as well as considering possible effect modifiers. The timing of genetic changes will also be identified in cases and controls using archived newborn blood samples from birth and buccal cells obtained at interview. For the case group, the [prevalence of specific molecular changes will be obtained from several specimen types (archived newborn blood, peripheral blood, peripheral blood and bone marrow at time of diagnosis, and buccal cell DNA at time of interview) in order to determine the timing of genetic changes. These changes will be stratified by parental self-reported exposures to identify if genetic changes in children correlate with self-reported parental exposures prior to birth or during pregnancy. This will demonstrate if exposures correlate with genetic changes and the temporal nature of occurrence of these changes. All new-diagnosed cases of childhood leukemia (ages 0-14 ) which present at one of the four referral hospitals in the Greater San Francisco Bay Area between 1995-1998 will be eligible (n=2000. Two matched controls groups will be obtained for each case; friend controls and birth certificate controls. Friend controls will be randomly chosen from nominees provided by parents that match the case on age, sex, gender, country of residence at diagnosis, and ethnicity of mother. Birth certificate controls will be chosen from California births that match the case with respect to age, sex, gender, county of birth, and ethnicity. Two questionnaires will be provided; a self-administered interview for parents to record dietary, occupational and residential histories three months prior to conception, during pregnancy, and up until diagnosis of index case. An in-person interview will then be scheduled to review data and collect additional information. Interviews will be in English and Spanish. This study offers particular design advantages over earlier studies due to use of two controls groups and in-person interview in two languages, and essentially a population-based case ascertainment for the Bay Area. However, the most important departure from other studies is the linking of the temporal aspect of genetic change with exposure that will lead to significant advances in understanding the etiology of childhood leukemia.