Grant Number:	5R03CA094770-02 Interpret this number
Primary Investigator:	Weisenburger, Dennis
Organization:	University Of Nebraska Medical Center
Project Title:	Case-Control Study of Pesticides and T(14;18) Lymphoma
Fiscal Year:	2003

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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