Diffuse Large B-Cell Lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL), accounting for approximately 30% of cases of NHL.1 According to the American Cancer Society, several factors increase the risk for NHL variants, including DLBCL.2


The incidence of DLBCL increases with age, as does that of many other lymphomas.2 The average age at the initial diagnosis of DLBCL is approximately 70 years.3


DLBCL is slightly more likely to develop in men than in women.2,4 The risk for mortality is also higher in men than in women when DLBCL is treated with standard rituximab regimens.3,5

Race/Ethnicity/Geographic Location

NHL, including DLBCL, occurs more frequently in developed countries.2 In the United States, DLBCL is more likely to develop in White individuals than in Black or Asian American individuals.2

Certain DLBCL subtypes that are linked to viruses or infections are more prevalent in specific geographical locations.2

Read more about DLBCL epidemiology

Family History

In general, DLBCL is not an inherited disease.4 However, the risk for NHL, including DLBCL, slightly increases if a first-degree relative has a history of NHL.2 Approximately 9% of patients with DLBCL have a first-degree relative (either a parent or sibling) with lymphoma or chronic lymphocytic leukemia.4

Autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, celiac disease, and other autoimmune disorders, may increase the risk for NHLs like DLBCL. When the immune system attacks the body’s own tissues, the overactivity results in increased lymphocyte production, heightening the likelihood of abnormal lymphocyte development.2

Patients with weakened immune systems are also more susceptible to the development of DLBCL. This can include individuals taking immunosuppressant medications following organ transplant, people with a genetic immunodeficiency syndrome, or individuals who acquire an infection that weakens the immune system, such as human immunodeficiency virus (HIV) infection.2


Some viruses transform lymphocytes by directly affecting their DNA, causing them to become cancer cells. Viruses that transform lymphocytes into cancerous white blood cells include Epstein-Barr virus (EBV), which is often linked to concomitant HIV infection, and human herpesvirus 8 (HHV8). Infection with EBV or HHV8 may result in the development of Burkitt lymphoma or primary effusion lymphoma, respectively.2,6,7 These viruses may also cause subtypes of DLBCL, including EBV-positive DLBCL and HHV8-positive DLBCL.7-9 A careful differential diagnosis is required because of the similarities between the lymphomas.

Read more about DLBCL types

Chronic infections caused by bacteria or viruses, such as Helicobacter pylori, Chlamydophila psittaci, hepatitis C virus, and Campylobacter jejuni, result in constant stimulation of the immune system. This process increases the production of lymphocytes and the risk for genetic mutations that lead to the development of lymphoma.2

Environmental Exposures

Exposure to certain chemicals or drugs (eg, benzene, herbicides, insecticides, specific chemotherapy drugs, and medications used to treat rheumatoid arthritis, including methotrexate and tumor necrosis factor inhibitors) has been linked to an increased risk for NHL. Patients with rheumatoid arthritis are already at a higher risk for NHL because of their autoimmune condition.2

Radiation exposure increases the likelihood of the development of many types of cancers, including NHL and leukemia. Additionally, the treatment of any type of cancer with a combination of radiation and chemotherapy may cause the subsequent development of NHLs such as DLBCL.2

Read more about DLBCL treatment

Body Weight

Excess body weight or obesity may increase the risk for NHL, including DLBCL. Poor diet and lack of exercise increase this risk.2 

Several sources suggest that increased consumption of fruits and vegetables and decreased consumption or avoidance of sugars, processed foods, and red meats reduce the likelihood of the development of DLBCL.2,10-12


  1. Gandhi S. Diffuse large B-cell lymphoma (DLBCL): practice essentials. Medscape. Updated May 6, 2021. Accessed August 20, 2022.
  2. Non-Hodgkin lymphoma risk factors. American Cancer Society. Accessed August 20, 2022.
  3. Epperla N, Vaughn JL, Othus M, Hallack A, Costa LJ. Recent survival trends in diffuse large B‐cell lymphoma––have we made any progress beyond rituximab? Cancer Med. 2020;9(15):5519-5525. doi:10.1002/cam4.3237
  4. Freedman AS, Friedberg JW. Patient education: diffuse large B-cell lymphoma in adults (Beyond the Basics). UpToDate. Updated July 22, 2022. Accessed August 20, 2022.
  5. Yıldırım M, Kaya V, Demirpençe Ö, Paydaş S. The role of gender in patients with diffuse large B cell lymphoma treated with rituximab-containing regimens: a meta-analysis. Arch Med Sci. 2015;11(4):708-714. doi:10.5114/aoms.2015.53289
  6. Burkitt lymphoma. Cancer Research UK. Accessed August 20, 2022.
  7. Narkhede M, Arora S, Ujjani C. Primary effusion lymphoma: current perspectives. Onco Targets Ther. 2018;11:3747-3754. doi:10.2147/OTT.S167392
  8. Murthy SL, Hitchcock MA, Endicott-Yazdani TR, Watson JT, Krause JR. Epstein-Barr virus–positive diffuse large B-cell lymphoma. Proc (Bayl Univ Med Cent). 2017;30(4):443-444. doi:10.1080/08998280.2017.11930222
  9. HHV8-positive diffuse large B-cell lymphoma, not otherwise specified. National Library of Medicine. Accessed August 20, 2022.
  10. Rohrmann S, Becker N, Linseisen J, et al. Fruit and vegetable consumption and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control. 2007;18(5):537-549. doi:10.1007/s10552-007-0125-z
  11. Chen GC, Lv DB, Pang Z, Liu QF. Fruits and vegetables consumption and risk of non-Hodgkin’s lymphoma: a meta-analysis of observational studies. Int J Cancer. 2013;133(1):190-200. doi:10.1002/ijc.27992
  12. Kelemen LE, Cerhan JR, Lim U, et al. Vegetables, fruit, and antioxidant-related nutrients and risk of non-Hodgkin lymphoma: a National Cancer Institute–Surveillance, Epidemiology, and End Results population-based case-control study. Am J Clin Nutr. 2006;83(6):1401-1410. doi:10.1093/ajcn/83.6.1401

Reviewed by Harshi Dhingra, MD, on 8/24/2022.