Trimodal age-specific incidence patterns for Burkitt lymphoma in the United States, 1973-2005

Abstract

Burkitt lymphoma (BL) is a unique B-cell non-Hodgkin lymphoma with 3 established clinical-epidemiological variants: endemic, sporadic and AIDS-related BL. BL variants show characteristic dysregulation of MYC gene, but the causes of MYC dysregulation or BL arising at different ages are poorly understood. Therefore, we examined population-based BL incidence patterns in the United States to determine age-related risk. BL case and population data were obtained from the NCI's Surveillance, Epidemiology and End Results Databases (1973-2005). Standard cross-sectional age-standardized and age-specific incidence rates were stratified by sex and race and supplemented with age-period-cohort models. We analyzed 3,058 BL cases diagnosed during 1,160,300,297 person-years of observation. Age-standardized incidence rates rose 6.8% per year (95% CI 4.5-9.1) for males and 7.1% (95% CI 3.2-11.1) for females during the study period. The rate among males was 3.2 times that among females, and among Whites 1.3 times that among Blacks. Male-to-female incidence rate ratios did not differ by race, but were 4.2 for pediatric (0-19 years), 4.1 for adult (20-59 years) and 2.0 for geriatric (> or = 60 years) BL. Cross-sectional age-specific rates showed 2 separate peaks among males and females, near ages 10 and 75 years, and a 3rd peak near age 40 years among males. The tri/bimodal incidence pattern was present in sensitivity analyses excluding registries with many HIV/AIDS cases and in period-specific, cohort-specific analyses. To our knowledge, tri/bimodal incidence patterns have not previously been reported for BL. Trimodal/bimodal BL suggests heterogeneity in etiology or biology of BL diagnosed at different ages in males and females.

Figure 1

Burkitt lymphoma male and female age-standardized incidence rates for males (solid squares) and females (open circles), also showing the estimated annual percentage change (EAPC) of the age-standardized incidence rate, (A) and age-specific incidence rates (B) in the United States by sex, SEER 9, 13, and 17 registries, 1974 through 2005. EAPC=estimated annual percentage change of the age-standardized incidence rate.

Figure 2

Burkitt lymphoma APC model-based expected period- and cohort-specific age-specific incidence rates by sex, SEER 9, 13, and17 registries, 1982 through 2005. Panels C and D included “fitted” age-at-onset curves (see methods). Cases diagnosed during 1973–1981 were excluded because of sparse numbers.

Figure 3

Burkitt lymphoma age, calendar-period, and birth-cohort deviations for males (solid squares) and females (open circles), based on age-period-cohort (APC) models, SEER 9, 13, and 17 registries, 1982 through 2005.

Figure 4

Kaplan-Meier BL-related mortality (Panels A–C) and hazard rates for BL-related deaths for males (solid lines) and females (dotted lines) (Panels D–F). BL related deaths included deaths from non-Hodgkin lymphomas and deaths from other infections and parasitic diseases related to HIV, SEER 9, 13, and 17 registries, 1974 through 2005.