Occupational Pesticide Use and Risk of Lymphoid Cancers

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 DESCRIPTION (provided by applicant): Exposure to pesticides is widespread, both in certain jobs and at lower levels in the home environment. There is a strong need for data quantifying cancer risks from pesticides, both for elucidating toxicologic mechanisms of carcinogenesis and for supporting regulation. There are studies suggesting that certain current-use pesticides may increase risk of non-Hodgkin lymphoma (NHL) and other lymphoid cancers such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM); however the size of individual studies hinders the ability to describe these associations with precision. Much larger numbers are needed to study risks of pesticide exposures, particularly for describing exposure-response relationships and risks for specific lymphoid cancer subtypes. We propose to conduct a powerful study of the risks associated with occupational pesticide exposures using the efficient approach of combining existing data resources from 10 case-control studies participating in the InterLymph Consortium and International Multiple Myeloma Consortium (IMMC). The pooled analysis will include over 11,000 cases and 12,000 controls with detailed questionnaire data on job history, farming, crops, livestock, pesticide use, application methods, personal protective equipment, and safety practices. Our study team will develop pesticide exposure matrices (PEMs) for each pesticide of interest with axes for job title, location, decade, crop, and livestoc. We will conduct exposure assessment with application of the PEMs, followed by review of additional detailed questionnaire data from each study to refine exposure probability and intensity for each pesticide. We will estimate the association of exposure to specific types of pesticides (e.g., organophosphate pesticides, pyrethroid insecticides, phenoxy herbicides) and pesticide active ingredients (e.g., chlorpyrifos, diazinon, malathion, permethrin, 2, 4-D, glyphosate) with risk of lymphoid cancers. We will also evaluate heterogeneity in estimated pesticide exposure effects between major lymphoid cancer subtypes. The InterLymph and IMMC consortia offer an outstanding setting to address our study aims, given the exceptionally large number of cases and previously harmonized data on pathology, occupation and covariates. Our effort in coding and harmonizing pesticide exposure variables across participating studies will develop a valuable resource for future consortia-based research, such as gene-environment analyses of pesticide exposure effects.