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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA158686-02
Application #
8515358
Study Section
Special Emphasis Panel (ZRG1-OBT-A (54))
Program Officer
Banez, Lionel L
Project Start
2012-07-23
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$190,284
Indirect Cost
$53,939
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Koff, Jean L; Flowers, Christopher R (2017) Prognostic modeling in diffuse large B-cell lymphoma in the era of immunochemotherapy: Where do we go from here? Cancer 123:3222-3225
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Bulka, Catherine; Nastoupil, Loretta J; Koff, Jean L et al. (2016) Relations Between Residential Proximity to EPA-Designated Toxic Release Sites and Diffuse Large B-Cell Lymphoma Incidence. South Med J 109:606-614
Glass, Samantha; Phan, Anh; Williams, Jessica N et al. (2016) Integrating understanding of epidemiology and genomics in B-cell non-Hodgkin lymphoma as a pathway to novel management strategies. Discov Med 21:181-8
Switchenko, Jeffrey M; Bulka, Catherine; Ward, Kevin et al. (2016) Resolving uncertainty in the spatial relationships between passive benzene exposure and risk of non-Hodgkin lymphoma. Cancer Epidemiol 41:139-51
Chen, Qiushi; Ayer, Turgay; Nastoupil, Loretta J et al. (2016) Population-specific prognostic models are needed to stratify outcomes for African-Americans with diffuse large B-cell lymphoma. Leuk Lymphoma 57:842-51
Koff, Jean L; Chihara, Dai; Phan, Anh et al. (2015) To Each Its Own: Linking the Biology and Epidemiology of NHL Subtypes. Curr Hematol Malig Rep 10:244-55
Chen, Qiushi; Ayer, Turgay; Nastoupil, Loretta J et al. (2015) Comparing the cost-effectiveness of rituximab maintenance and radioimmunotherapy consolidation versus observation following first-line therapy in patients with follicular lymphoma. Value Health 18:189-97
Chihara, Dai; Nastoupil, Loretta J; Williams, Jessica N et al. (2015) New insights into the epidemiology of non-Hodgkin lymphoma and implications for therapy. Expert Rev Anticancer Ther 15:531-44
Williams, Jessica N; Koff, Jean L; Flowers, Christopher R (2015) Reply to Treatment decisions and outcome in very elderly patients with diffuse large B-cell lymphoma. Cancer 121:3748

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