Epidemiology and etiology of diffuse large B-cell lymphoma

Abstract

As the most common non-Hodgkin lymphoma subtype, diffuse large B-cell lymphoma (DLBCL) incidence patterns generally parallel that for NHL overall. Globally, DLBCL accounts for a third of all NHLs, ranging between 20% and 50% by country. Based on United States (U.S.) cancer registry data, age-standardized incidence rate for DLBCL was 7.2 per 100,000. DLBCL incidence rises with age and is generally higher in males than females; in the U.S., incidence is highest among non-Hispanic whites (9.2/100,000). Like NHL incidence, DLBCL incidence rose in the first half of the 20th century but has largely plateaued. However, there is some evidence that incidence rates are rising in areas of historically low rates, such as Asia; there are also estimates for rising DLBCL incidence in the near future due to the changing demographics in developed countries whose aging population is growing. Established risk factors for DLBCL include those that result in severe immune deficiency such as HIV/AIDS, inherited immunodeficiency syndromes, and organ transplant recipients. Factors that lead to chronic immune dysregulations are also established risk factors, and include a number of autoimmune conditions (eg, Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis), viral infections (eg, HIV, KSHV/HHV8, HCV, EBV), and obesity. Family history of NHL/DLBCL, personal history of cancer, and multiple genetic susceptibility loci are also well-established risk factors for DLBCL. There is strong evidence for multiple environmental exposures in DLBCL etiology, including exposure to trichloroethylene, benzene, and pesticides and herbicides, with recent associations noted with glyphosate. There is also strong evidence for associations with other viruses, such as HBV. Recent estimates suggest that obesity accounts for nearly a quarter of DLBCLs that develop, but despite recent gains in the understanding of DLBCL etiology, the majority of disease remain unexplained. An understanding of the host and environmental contributions to disease etiology, and concerted efforts to expand our understanding to multiple race/ethnic groups, will be essential for constructing clinically relevant risk prediction models and develop effective strategies for disease prevention.

Keywords: DLBCL; Epidemiology; Etiology; Lymphoma; Risk factors.

Fligure 1.

Trends in DLBCL incidence by race and sex, 12 SEER registries, 1992–2020. Presented for 6 fixed time periods (1992–1996, 1997–2001, 2002–2006, 2007–2011, 2012–2016, 2017–2020)

FIGURE 2.

DLBCL incidence by age, race and sex, 12 SEER registries, 2011–2020. All incidence rates are age-adjusted to the 2000 United States population.