Host factors and etiology of leukemia

描述：个体表现出相当大的差异，在他们的能力， 代谢治疗药物，并在代谢潜在的毒性 环境中存在的化学物质。这种变化在很大程度上是由于 基因差异（多态性）参与解毒或 对基因损伤的反应初步数据表明，多态宿主 因素是重要的，在响应白血病治疗，在病因学， 白血病，并在治疗并发症的发生。总体目标 这项提议的一个重要目的是从患有 细胞遗传学良好表征和统一治疗的白血病，并使用 分析影响白血病治疗结果的宿主因素 以及白血病的病因学本研究是一项相关研究， 并扩大NCI资助的儿童肿瘤组（COG）化疗治疗 审判在这项研究中，我们将检查多态性位点的等位基因频率， 参与药物代谢、DNA修复、DNA合成和 参与COG治疗研究的儿童对氧化损伤的防御。 将对数据进行分析，以确定这些位点的等位基因变异 影响治疗的结果。此外，等位基因频率将 与正常人群相比，以确定他们是否 影响白血病易感性。最后，收集到的DNA将作为 影响治疗并发症的多态性研究资源 例如继发性癌症、骨缺血性坏死和血栓形成事件。

DESCRIPTION: Individuals show considerable variation in their ability to metabolize therapeutic drugs, and in the metabolism of potentially toxic chemicals occurring in the environment. The variability is due in large part to genetic differences (polymorphisms) in genes involved in detoxification or in the response to genetic damage. Preliminary data indicate that polymorphic host factors are important in response to leukemia treatment, in etiology of leukemia, and in the occurrence of complications of treatment. The overall aim of this proposal is to develop a DNA resource from children with cytogenetically well characterized and uniformly treated leukemia, and to use it to analyze host factors influencing the outcome of treatment for leukemia and the etiology of leukemia. This study is a correlative study complementing and expanding NCI funded Children's Oncology Group (COG) chemotherapy treatment trials. In this investigation we will examine allele frequencies at polymorphic sites in genes involved in drug metabolism, DNA repair, DNA synthesis and in defense against oxidant damage in children enrolled on COG therapeutic studies. The data will be analyzed to determine whether allelic variation at these sites influence the outcome of therapy. In addition, allele frequencies will be compared with those seen in normal population to determine whether they influence susceptibility to leukemia. Lastly, the DNA collected will serve as a resource for studies of polymorphisms which influence complications of therapy such as second cancers, avascular necrosis of bone and thrombotic events.