This proposal is to study the long term health of children treated for Wilms tumor (WT), and to monitor their offspring for cancer and birth defects. The study is based in the unique and well described cohort of 9,236 patients enrolled during 1969-2002 on one of 5 clinical trials conducted by the National Wilms Tumor Study (NWTS). NWTS studies 3-5 developed treatment protocols that today are administered as "standard therapy" to the vast majority of patients. With this therapy, 90% of children with WT are cured. Survivors, however, are at risk for delayed complications of their disease or its treatment that may compromise their quality of life. Since the disease typically occurs in early childhood, many decades of follow-up are required to appreciate the consequences for adult survivors. Four life-threatening conditions are targeted: secondary malignant neoplasms;congestive heart failure;end stage renal disease (ESRD);and restrictive pulmonary disease. Most occurrences are validated by examination of medical records. Specific goals are to identify new subgroups of patients from NWTS-3-5 at high risk for each condition based on treatment, disease and host factors. Patients at high risk for ESRD, for example, may be considered for renal sparing surgery. Biological samples collected from patients on NWTS-5 will be used to test the hypothesis that mutations in the WT1 gene not only predispose to WT in childhood but also to ESRD in adolescence and adulthood. Systematically collected information on birth weights, congenital anomalies, nephrogenic rests, histologic type, and on radiation and chemotherapy doses will be used to construct risk functions for ESRD and to investigate whether treatment effects on congestive heart failure and secondary malignant neoplasms differ according to the biological subtype of Wilms tumor. The study will estimate rates of ovarian failure in female patients and rates of live birth and risks of pregnancy complications in partners of male patients. Heritability and recurrence risks of WT, together with the frequency of birth defects in the next generation, will be estimated through follow-up of a unique cohort of patient offspring.
By elucidating the late complications of WT and its treatment, and by identifying susceptible subgroups, this study will enable future generations of childhood cancer patients and their physicians to select optimum treatments based on knowledge of long term risks as well as short term benefits. It will assist survivors to make informed decisions regarding the risks of pregnancy and the likelihood that their children will also develop Wilms tumor or birth defects.
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