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Cancer Control Research

5R01CA079457-04
Buckley, Jonathan D.
PESTICIDES AND VDJ-RECOMBINASE MUTATIONS IN CHILD NHL

Abstract

DESCRIPTION: (Adapted from Investigator's Abstract) Pesticide exposures are associated with increased risk of lymphoma and leukemia in adults. The Children's Cancer Group (CCG) recently found non-Hodgkin's lymphoma (NHL) in the child and parent to be associated with pesticide exposure. The chromosomal effects appear to be due to aberrant action of the VDJ-recombinase system relative to rearrangements of the genome coding for immunoglobulins and T-cell receptor proteins. These rearrangements were increased in pesticide-exposed agricultural workers. This application proposes to conduct a case-control study of childhood NHL (600 newly-diagnosed cases of unspecified gender) to (1) confirm the elevated risk with pesticide exposure, identify the types of pesticides responsible, and determine the relative importance of in utero versus childhood exposure, and (2) use two blood biomarkers of aberrant VDJ-recombinase activity to determine whether children with NHL have higher rates of recombination than control subjects, and whether these frequencies correlate with pesticides (pre-), other environmental exposures (pre-), and effectiveness of chemotherapy (post-). Two matched control groups will be identified and a community control (random digit dialing) and a control ascertained through the case's treating institution. The investigators state that the results will be potentially relevant to childhood leukemia as well as lymphoma, and may also have implications for these malignancies in adults.

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