This is a competing renewal application for a case-control study of childhood Hodgkin's disease (HD) with epidemiologic, genetic and virologic components. Cases are from the Children's Cancer and Pediatric Oncology Groups with individually matched controls selected by random digit dialing (RDD). Epidemiologic data for 480 cases and 726 matching controls have been collected by telephone interviews of parents. Tumor specimens have been collected for 321 cases and blood samples for 234 cases for Epstein-Barr virus (EBV) studies. In the new phase of this study, emphasis will be placed on genetic factors in the etiology of HD. Thus far, 186 case and 79 control families have been re-interviewed. Complex segregation analyses of the family data have been performed and the best fit is with an environmental rather than a Mendelian inheritance model of HD using two approaches. DNA microsatellite markers will be used to test for the association between HD and candidate HLA regions and non-HLA regions. The second approach will perform high resolution molecular typing HLA Class I (HLA-A,B,C) and II (HLA-DR, DQA1, D1B1 and DP) alleles. The proposed HLA studies will allow for analyses of the relationship between EBV-status and subject's HLA type. The proposed new studies will also include statistical assessment of time-space clustering of cases and controls, an evaluation of the introduction of socioeconomic status bias by RDD and the performance of a second follow-up interview of subjects' families. The study will focus on Hispanic cases since they differ significantly from other cases in EBV-positivity of their tumors and other epidemiologic features.
