Although multiple myeloma is clinically defined as the accumulation of clonal, malignant plasma cells in the bone marrow, the disease shows significant heterogeneity with regard to progression and therapeutic response. The hypothesis addressed in this proposal is that functional genetic polymorphisms are associated with tumor growth control, drug metabolism/detoxification, and DNA repair mechanisms that will influence chemotoxicity and the course of the disease. Cell and DNA banks from 3 phase Ill clinical trials of the Eastern Cooperative Oncology Group will be used to determine allelic frequencies of genetic polymorphisms in genes associated with drug metabolism/transport (cytochrome P450, myeloperoxidase, glutathione S-transferases (M,T,P), multi-drug resistance 1); DNA repair (XRCCC1, ERCC2); and, myeloma related growth factors (lL-6, IL-1b, IL-1RA, IL-10, TNa, Lta, TGFb). Known genetic polymorphisms that alter function of each of these gene products will be correlated with survival, bone disease, toxicity, response, infection, and secondary malignancies. These correlations will provide important genetic markers that will allow better individualized treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA096609-01
Application #
6506169
Study Section
Clinical Oncology Study Section (CONC)
Program Officer
Tricoli, James
Project Start
2002-07-08
Project End
2004-06-30
Budget Start
2002-07-08
Budget End
2003-06-30
Support Year
1
Fiscal Year
2002
Total Cost
$148,500
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Genetics
Type
Schools of Arts and Sciences
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455