EXPOSURE TO MEDICAL RADIATION AND AML FAB SUBTYPE

描述(申请人描述)：AML是最常见的成人起病白血病，也是最迅速致死的，然而这种毁灭性疾病的病因仍然很大程度上仍不清楚。电离辐射，如医用X射线，已被证明可引起急性髓细胞白血病，并在严重暴露的人群中定义了剂量反应，尽管敏感度仍然难以捉摸。对相对较低剂量暴露后的急性髓系白血病的研究很少，而且不一致。我们有了令人兴奋的新发现，这表明相对较低的放射暴露与AML亚型M4和M5有关。这两种类型也与11q23区域的细胞遗传学异常有关。11q23是AT基因的位置，当暴露在辐射中时，它似乎使携带者更容易发生各种癌症。我们建议在一项对新诊断病例的独立研究中确认亚型特异性与放射学的相关性，并调查这种相关性是否与似乎患有放射源性AML的M4/M5患者中ATM携带者状态的患病率高于预期有关。这项拟议的研究将包括从1999年到2003年诊断的310例洛杉矶县成人AML病例。病例将按出生年份、种族和性别与对照进行邻里匹配。委托书将用于无法面谈的案件。为我们目前的研究开发的剂量学模型将被用于分配诊断X射线的曝光量。ATM杂合率将在按医疗辐射暴露水平和FAB亚型定义的组之间进行比较。吸烟和其他潜在的危险因素也将被调查。FAB亚型特异性分析似乎对进一步阐明AML的病因至关重要。查明对特定暴露(如大气压和电离辐射)的遗传易感性将有助于查明可能可预防的急性髓系白血病病例。

DESCRIPTION (Applicant's Description): AML is the most common adult-onset leukemia and the most rapidly fatal, yet the etiology of this devastating disease remains largely unknown. Ionizing radiation, such as from medical x-rays, has been shown to cause AML and dose- response has been defined in heavily exposed populations, although susceptibility has remained elusive. Studies of AML after relatively low dose exposures have been few and inconsistent. We have exciting new findings which suggest that the association with relatively low radiographic exposure is specific to AML subtypes M4 and M5. Both types are also associated with cytogenetic abnormalities in the 11q23 region. 11q23 is the location of the AT gene which appears to predispose carriers to the development of various cancers when exposed to radiation. We propose to confirm the subtype-specific association with radiography in an independent study of newly diagnosed cases and to investigate whether the association may relate to a higher than expected prevalence of ATM carrier status in M4/M5 patients who appear to have radiogenic AML. The proposed study will include 310 Los Angeles County adult-onset AML cases, diagnosed from 1999 through 2003. Cases will be neighborhood-matched to controls by birth year, race, and gender. Proxies will be used for cases unavailable for interview. Dosimetry models developed for our current study will be used to assign exposure from diagnostic x-rays. ATM heterozygosity rates will be compared between groups defined by level of exposure to medical radiation and by FAB subtype. Smoking and other potential risk factors will also be investigated. FAB subtype-specific analyses appear essential to further elucidate the etiology of AML. Identification of genetic susceptibility to particular exposures (e.g., ATM and ionizing radiation) would enable the identification of potentially preventable cases of AML.