Cancer Control Research
5R01CA079457-05
Buckley, Jonathan D.
PESTICIDES AND VDJ-RECOMBINASE MUTATIONS IN CHILD NHL
AbstractDESCRIPTION: (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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