This is a revised proposal for the long term follow-up of survivors from the National Wilms' Tumor Study (NWTS) and their offspring so as to elucidate the genetic origins of Wilms' tumors, to estimate the risk of adverse pregnancy outcomes and congenital defects and to determine the rates of second tumors and heart disease in patients treated for cancer in childhood. The NWTS is a large collaborative trial organized in 1969 that currently registers an estimated 70% or more of the children diagnosed with Wilms' tumor in the United States. Patients are followed on the clinical trial for five years from diagnosis, by which time those who have survived may be considered cured of their initial disease. This proposal is to develop and implement efficient means of continued follow-up beyond five years so that the lessons to be learned from this invaluable cohort of children and young adults will not be lost to science, and to perfect these methods as a model for others engaged in similar studies. Late effects to be ascertained in this longitudinal study include second malignant tumors, benign tumors, serious heart disease, reproductive outcomes, and congenital defects and cancer, including familial Wilms' tumors, that may develop in offspring. The treatment interventions used in the NWTS are combinations of four chemotherapeutic agents with and without radiation therapy. This will permit the comparison of rates of occurrence of key events among randomized patient subgroups that differ with respect to the use and dosage of radiation therapy and the specific type of chemotherapy. Data on Wilms' tumors in family members and offspring will be collected so as to determine the population frequency, degree of dominance and penetrance of the putative """"""""Wilms' gene"""""""" and to assist others in the location of the gene or genes via linkage analysis. Data on late effects will be analyzed according to type and duration of therapy, years elapsed since initiation of treatment, age and host factors. Patients will be followed by means of an automated system that maintains annual contact with survivors and actively pursues those patients and families who become lost to follow-up. Information on health status and other key events will be obtained from periodic physical exams and medical histories, with questionnaires and reviews of medical records used to obtain details on reproductive outcomes and diagnoses of key medical conditions.
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