The resource represented by the Childhood Cancer Survivor Study (CCSS) is the result of a multi-institutional collaborative project, which has established and followed a retrospectively ascertained cohort of over 14,000 five year survivors of childhood cancer diagnosed between 1970 and 1986 and over 6000 sibling controls. Members of the cohort, currently ranging in age from 11 to 48 years (median age 26 years) have provided information encompassing over 200,000 person-years of follow- up since diagnosis of the original cancer. This population represents a large and heterogenous group of childhood cancer survivors treated in a fashion that has direct relevance to most current heterogenous group of childhood cancer survivors treated in a fashion that has direct relevance to most current therapeutic strategies. This characteristic, in combination with the high rate of participation, the extensive characterization of participants' prior therapy, and attention to collection of high quality data, makes the CSS an outstanding and, indeed, unique national resource for the conduct of innovative research. The objectives of this competitive renewal application, which reflects a conversion from a U01 to U24, are to (1) expand the research questions posed in the original grant application by extending the length of follow-up of this unique population with questions posed in the original grant application by extending the length of follow-up of this unique population with approximately 65,000 additional person-years; (b) strengthen the resource by establishing repositories for biological specimens to facilitate future molecular biologic investigations; (c) maintain the current consortium of investigators from specimens to facilitate future molecular biologic investigations; (c) maintain the current consortium of investigations from the 25 participating centers in the United States and Canada, who provide scientific expertise and facilitate ongoing activities; (d) serve as a source of ongoing education for the survivor population; and (3) continue to be a resource for innovative investigator-initiated studies of childhood cancer survivors. These objectives will be achieved through specific aims: (1) continued follow-up and interaction with members of the cohort to educate and ascertain key outcomes; (2) collection and storage of biologic specimens consisting of tumor specimens from subsequent neoplasms, buccal cells as a source of genomic DNA on all members of the cohort, a and peripheral blood for establishment of lymphoblastoid cell lines for survivors who develop a subsequent neoplasm or have a known genetic condition associated with cancer risk; and (3) facilitate the use of the CCSS resource to address important questions related to cancer survivorship including the development and testing of intervention strategies. The CCSS provides a dynamic framework and resource in which to investigate current and future questions regarding consequences of therapy, genetic associations, disease processes and causation, interventions, and quality of life among childhood cancer survivors.