Host factors and etiology of leukemia

描述：个体在能力上表现出相当大的差异 代谢治疗药物，并在代谢中潜在的毒性 存在于环境中的化学物质。这种可变性在很大程度上是由于 与解毒有关的基因的遗传差异(多态) 对基因损伤的反应。初步数据表明，多态宿主 在白血病治疗的反应中，因素是重要的，在病因中 白血病，并在治疗过程中发生并发症。总体目标 这项提议的目的是开发一种来自患有 细胞遗传学特征良好且统一治疗的白血病，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。本研究是对相关研究的补充 和扩大NCI资助的儿童肿瘤学小组(COG)化疗 审判。在本次调查中，我们将检测多态基因的等位基因频率。 基因中涉及药物代谢、DNA修复、DNA合成和 参加COG治疗研究的儿童对氧化损伤的防御。 将对数据进行分析，以确定这些位点上的等位基因变异 影响治疗的结果。此外，等位基因频率将是 与正常人群相比，以确定他们是否 影响白血病的易感性。最后，收集到的DNA将作为 研究影响治疗并发症的多态的资源 例如第二次癌症、骨缺血性坏死和血栓事件。

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.