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.
