DESCRIPTION (provided by applicant):
A population-based, case-control study of non-Hodgkin's lymphoma (NHL) was
conducted in Nebraska between 1983 and 1986. This NCI's study collected
extensive information on agricultural exposures. Herein, an ancillary
molecular study is proposed to determine the role of pesticides in the
occurrence of t(14;18) chromosomal translocation in this case-control study.
An association between NHL and pesticides has been observed repeatedly, but
not consistently. Results of epidemiologic studies of pesticides and NHL may
be obscured by the aggregate evaluation of cases that are etiologically
diverse. The t(14;18) is the most common cytogenetic abnormality, and
t(14;18)-mediated constitutive overexpression of BCL2 protein is an important
early event in NHL pathogenesis. The current proposal will classify NHL cases
according to t(14;18) status to identify agricultural risk factors that may be
specifically associated with t(14;18)-positive or -negative pathogenic
mechanisms. The specific aims are to 1) obtain paraffin-embedded tumor blocks
for NHL cases; 2) determine the presence of the t(14;18) translocation; and 3)
investigate pesticides for their association with t(14;18)-positive NHL or
t(14;18)-negative NHL. The hypothesis is that pesticides act specifically
along a t(14;18)-dependent pathway, resulting in stronger associations with
t(14;18)-positive than t(14;18)-negative NHL. The research design is a
molecular case-control study. Tumor blocks will be obtained from the Lymphoma
Registry Tissue Bank for all NHL cases in the original case-control study
(about 270-290 tissue blocks will be available). Fluorescence in-situ
hybridization (FISH) analysis will be used to determine the presence of the
t(14;18) translocation. Results from FISH analyses will be used to classify
NHL cases into t(14;18)-positive NHL or t(14;18)-negative NHL. Logistic
regression models will be used to calculate the odds ratios for
t(14;18)-positive NHL and t(14;18)-negative NHL associated with various groups
and types of pesticides. The low-term objective is to improve understanding of
the disease process which may ultimately lead to improved prevention of NHL in
the general population.
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