Hodgkin lymphoma (HL) is the first and second most common cancer among young women and men 20-39 years old, respectively. Our previous results from a small twin study suggested that an inherited imbalance in the immune response to infection could increase susceptibility to young adult HL. Here we will further test the hypothesis that the susceptible immunophenotype for HL is determined by a genetic tendency toward an exaggerated Th2 and/or inflammatory response and/or a depressed Th1 response, resulting from genotypes that regulate these responses. After 10 months of harmonizing the IRB materials between USC and the DOD, we have begun data collection. To date we have obtained and processed blood and saliva samples for DNA from 221 patients plus their parents to serve as controls. We will begin genotyping when we collect the projected 368 cases plus their parents or siblings (controls). With one more year in the field, we expect to reach our goal of 378 case-family sets. If we can identify the immune pathways responsible for this cancer, we may be able to design immunotherapy to prevent it, avoiding many lost years of productivity and loss of life that results from the treatment and its complications.