Grant Number:	7R03CA132153-03 Interpret this number
Primary Investigator:	Chiu, Brian
Organization:	University Of Chicago
Project Title:	Risk Factors for Molecularly Defined Subgroups of Lymphoma: a Pooled Analysis
Fiscal Year:	2008

DESCRIPTION (provided by applicant): The chromosomal translocation t(14;18)(q32;q21) is one of the most common chromosomal abnormalities in non-Hodgkin lymphoma (NHL). Although the t(14;18) has important clinical ramifications, its etiologic significance remains to be determined. Two recent population-based case-control studies (one in Iowa/Minnesota and the other in Nebraska) addressed this issue by evaluating potential risk factors for t(14;18)-positive and t(14;18)-negative subgroups of NHL. Findings from these two studies indicate that the causes of t(14;18)-positive NHL differ from those of t(14;18)-negative NHL. However, sample sizes of the Iowa/Minnesota and Nebraska studies limited the precision and detail of effect estimate measures. Therefore, we propose a pooled analysis of existing data from these two studies with similar study design and data collection instruments. The central innovative hypothesis is that risk factors differ for discrete subsets of NHL defined by t(14;18) status. The specific aims are to investigate whether the associations with pesticides, family history of hematopoietic cancer, and solvents differ for t(14;18)-defined subgroups of NHL. A total of 327 cases with data on t(14;18) status and 2,677 population-based controls will be available for the pooled analysis. The t(14;18) was determined by the fluorescence in-situ hybridization (FISH) technique in both the Iowa/Minnesota and Nebraska studies. Subtypes of NHL will be defined by the presence or absence of the t(14;18). Logistic and polytomous regression models will be used to estimate the associations between exposures and risk of t(14;18)-defined subtypes of NHL and to compare odds ratios for t(14;18)-positive NHL with odds ratios for t(14;18)-negative NHL. Hierarchical regression will be used to estimate the risk of t(14;18)-positive or t(14;18)-negative NHL associated with specific pesticide exposure. The results will be significant because they will provide new insights into disease etiology. The long-term objective is to improve our understanding of etiopathogenesis of NHL so that we may ultimately identify risk factors that can be modified to reduce the incidences of NHL in the general population. Because the study population is well-characterized and data on the t(14;18), pesticides, and other exposures have already been collected, the proposed study is extremely cost-effective for addressing the etiology of NHL, one of the most common malignancies in this country. Non-Hodgkin lymphoma (NHL) is the fifth most common cancer in the United States, but the causal factors are largely unknown. Recurring chromosomal abnormalities are a hallmark of NHL. Of the numerous chromosomal abnormalities, the t(14;18) is the most common one. Findings from two recent epidemiologic studies conducted in Iowa/Minnesota and Nebraska suggest that the causes of t(14;18)- positive NHL differ from those of t(14;18)-negative NHL. However, the sample size for the individual studies is not large enough for extensive statistical analysis. To address this issue, we propose a pooled analyses of data from these two studies, resulting a total of 327 cases with data on t(14;18) status and 2,677 population-based controls. The large sample size allows us to evaluate the strength and consistency of the associations between exposures and risk of t(14;18)-defined subgroups of NHL. The long-term objective is to improve our understanding of development of NHL so that we may ultimately identify risk factors that can be modified to reduce the occurrences of NHL in the general population. This project directly responds to the NCI strategic plan for cancer preemption because it can elucidate the etiology of NHL.





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