The Role of Activation-Induced Cytidine Deaminase in Pesticide-Related Lymphomagenesis

Agricultural workers, military personnel, and the general population experience significant exposure to pesticides, including herbicides, fungicides, and insecticides, over their lifetime. Several epidemiologic studies have shown that pesticide exposure increases the risk of certain types of non-Hodgkin B cell lymphoma. The biological reasons for this increased risk, as well as the types of chemicals that affect lymphoma risk, are not well understood. The overarching goal of this proposal is to clarify the causal link between pesticide exposure and the development of lymphoma, therefore allowing for identification of specific chemicals that increase lymphoma risk, identifying possible biomarkers useful in evaluation of at risk populations, and enabling prevention of exposure-related lymphoma. The results of these studies will improve understanding of lymphoma risk, with important implications for public health and lymphoma prevention. This work will benefit military personnel in particular because they experience significant occupational exposure to a large variety of pesticides in the course of their service and have demonstrated pesticide exposure-related health effects, including increased lymphoma risk (in the case of exposure to Agent Orange, a blend of herbicides used during the Vietnam War, for example).

The Principal Investigator on this proposal is Rebecca Leeman-Neill, MD, PhD, a hematopathologist and assistant professor at Columbia University Medical Center who has a background in lymphoma, environmental exposure-related cancers, cancer prevention, and cancer genetics. Her overall career goal is to contribute to our knowledge of the basis of environmental risk factors for lymphoma with the goal of improving cancer prevention and public health. The topic of the studies proposed requires a complex skill set, including expertise in environmental exposures, genomics, immunology, molecular cancer biology, and pathology. Therefore, Dr. Leeman-Neill has assembled a multidisciplinary team of mentors and collaborators. Her training plan includes a combination of didactic learning in the areas of lymphoma research, cancer genetics, immunology, and environmental health and hands-on experience with research methodologies with which she hopes to gain experience and expertise. Funding of this study will be critical in allowing Dr. Leeman-Neill the resources to lay the groundwork for her career as an independent physician scientist investigating the important but relatively neglected area that is the topic of this proposal.