Host factors and etiology of leukemia

白血病的宿主因素和病因

• 批准号: 6415003
• 负责人: Stella Margaret Davies
• 金额: $ 32.65万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-18 至 2002-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6415003
• 关键词: DNA repair; DNA replication; acute lymphocytic leukemia; acute myelogenous leukemia; adolescence (12-20); alleles; child (0-11); clinical research; disease /disorder etiology; drug metabolism; gene frequency; genetic polymorphism; genetic susceptibility; human subject; neoplasm /cancer genetics; oxidative stress; pediatric neoplasm /cancer

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.

描述：个人表现出很大的差异 代谢治疗药物，并在潜在有毒的代谢中 化学物质发生在环境中。可变性在很大程度上是由于 参与排毒或中的基因中的遗传差异（多态性） 对遗传损害的反应。初步数据表明多态宿主 对于对白血病治疗的响应，因素在病因学中很重要 白血病，以及治疗并发症的发生。总体目标 该建议的是从儿童开发DNA资源 细胞遗传学特征良好且均匀治疗的白血病，并使用 它可以分析影响白血病治疗结果的宿主因素 以及白血病的病因。这项研究是一项相关的研究补充 并扩大NCI资助的儿童肿瘤学组（COG）化学疗法治疗 试验。在这项调查中，我们将检查多态性的等位基因频率 参与药物代谢，DNA修复，DNA合成和中的基因的位点 参加COG治疗研究的儿童中氧化剂损害的防御。 将分析数据以确定这些位点上的等位基因变化是否 影响治疗的结果。此外，等位基因频率将是 与正常人群中看到的人相比 影响对白血病的易感性。最后，收集的DNA将用作 影响治疗并发症的多态性研究资源 例如第二癌，骨骼和血小板事件的无血管坏死。