Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in the US, affecting ~22,000 people/year. If untreated 92% of DLBCL die within 1 year, however, with modern combinations of chemotherapy and immunotherapy >50% of patients are cured, making DLBCL a clinically significant disease for examining cancer disparities. We discovered that black patients with DLBCL in the United States, are diagnosed at an age a decade younger age than whites (average age 53 vs. 70 years), are more likely to have advance stage disease, be uninsured or Medicaid insured, reside in the lowest socioeconomic status areas, and are less likely to have received modern chemotherapy. We confirmed these differences in age and stage in a second US population-based data set, and found blacks also had worse 5-year survival (38% vs. 46%). However, in separate studies at Emory and University of Alabama-Birmingham (UAB) and our combined study, we found again that black patients presented at a significantly younger age and still had worse survival even when the exact same treatment was given. Two biologically different subtypes of DLBCL can be identified that have different survival, Germinal center B-cell (GCB) DLBCL: 60% 5-year survival and activated B-cell (ABC) DLBCL: 35%. We propose to examine relationships between these biological variants and racial differences in DLBCL. Based on a widespread analysis of genes in DLBCL tumors and matched normal tissue, we helped identified 15 genes that are differentially mutated in ABC and GCB DLBCL and seek to determine if these differ by race. The main aims are: 1) To examine racial differences in the prevalence of ABC-like DLBCL and explore the relationships between ABC subtype, race and survival, and 2) To examine racial differences in novel genes differentially mutated in ABC-like DLBCL. We identified 433 DLBCL patients from the Emory and UAB cohort studies with available tissue blocks and clinical data. We are collecting demographic, insurance, employment, treatment, response and survival data, will construct a tissue microarray, and will perform IHC subtyping, mutation and expression profiling.

Public Health Relevance

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in the US, affecting ~22,000 people/year. If left untreated nearly all patients live less than one year, however, with modern combinations of chemotherapy and antibody therapy more than 50% of patients are cured of their lymphoma, making DLBCL an ideal disease for studying cancer disparities. We discovered that black patients with DLBCL are diagnosed at a younger age than whites, more likely to have advanced stage disease, and have worse survival even when the same treatment is given, and want to determine whether a poor risk biological subtype of DLBCL is more common in black patients.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-OBT-A (54))
Program Officer
Banez, Lionel L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Emory University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Read, Jay A; Koff, Jean L; Nastoupil, Loretta J et al. (2014) Evaluating cell-of-origin subtype methods for predicting diffuse large B-cell lymphoma survival: a meta-analysis of gene expression profiling and immunohistochemistry algorithms. Clin Lymphoma Myeloma Leuk 14:460-467.e2
Flowers, Christopher R; Shenoy, Pareen J; Borate, Uma et al. (2013) Examining racial differences in diffuse large B-cell lymphoma presentation and survival. Leuk Lymphoma 54:268-76
Bulka, Catherine; Nastoupil, Loretta J; McClellan, William et al. (2013) Residence proximity to benzene release sites is associated with increased incidence of non-Hodgkin lymphoma. Cancer 119:3309-17
Nastoupil, Loretta J; Sinha, Rajni; Flowers, Christopher R (2013) The role of chemotherapy in managing chronic lymphocytic leukemia: optimizing combinations with targeted therapy. Expert Rev Anticancer Ther 13:1089-108
Flowers, Christopher R; Pro, Barbara (2013) Racial differences in chronic lymphocytic leukemia. Digging deeper. Cancer 119:3593-5
Ambinder, Alexander J; Shenoy, Pareen J; Nastoupil, Loretta J et al. (2013) Using primary site as a predictor of survival in mantle cell lymphoma. Cancer 119:1570-7
Nooka, Ajay K; Kaufman, Jonathan L; Behera, Madhusmita et al. (2013) Bortezomib-containing induction regimens in transplant-eligible myeloma patients: a meta-analysis of phase 3 randomized clinical trials. Cancer 119:4119-28