The central hypothesis of this proposal is that subtype specific analyses of non-Hodgkin's lymphoma will reveal associations that were previously masked, either partially or fully, by the practice of combining across etiologically heterogeneous diseases. Previously investigations of non-Hodgkin's lymphoma have generally lumped all lymphoma subtypes together due to sample size constraints and lack of pathologic review. There is a growing consensus among investigators that the non-Hodgkin's lymphomas represent a collection of etiologically distinct diseases and that an effort should be made to study disease entities separately. The Selected Cancers Study, a large case control study of non-Hodgkin's lymphoma (N=1157) and other cancers that included a detailed exposure assessment and pathologic review, presents the opportunity to perform powerful subtype analyses. The investigators propose to investigate patterns of risk in subtypes and groupings of subtypes in this database. While attention will be focused on environmental and occupational exposures that have previously been reported to be associated with all non-Hodgkin lymphomas combined (e.g., herbicides, leather, meat, solvents, formaldehyde, asbestos, radiation, EMF), an exploratory analysis will likely generate new hypotheses. Confirmation of observed patterns will subsequently be sought in a pooled analysis combining data from previous, smaller case control studies. This proposal includes methodologic work to improve the accuracy of risk and confidence interval estimation in the proposed analyses combining data from previous, smaller case control studies. This proposal includes methodologic work to improve the accuracy of risk and confidence interval estimation in the proposed analyses, using exact logistic regression and adjustment for uncertainty in exposure variables. As time allows, a similar approach is planned for studying sarcoma, a second group of cancers included in the Selected Cancers Study. Preliminary analysis of non-Hodgkin's lymphoma subtypes in the Selected Cancers Study database has already indicated striking subtype specificity of risk factors. The non-Hodgkin's lymphomas have shown an unexplained rise in incidence in the past several decades, and by performing a thorough investigation of risk factor for subtypes of lymphoma, the investigators hope to contribute importantly to the understanding of the etiology of this group of diseases.
