ES demonstrates differential incidence according to race. People of European ancestry are much more frequently affected compared to people of African and East Asian ancestry (12, 13). In addition, differences in clinical presentation and outcome by race have been previously demonstrated in this disease (14). The impact of race on the incidence of other mesenchymal tumors associated with EWSR1 translocations has not been studied.

ICD-O-2 and ICD-O3 diagnosis codes were used to identify patients diagnosed with ES (9260/3), CCS (9044/3), EMC (9231/3), and MLPS (8852/3) from 1973 – 2007 (19). The search for cases of DSRCT (8806/3) and ME tumors (8982/3) began in the year in which these entities were first described (1991 and 1997, respectively) and ended in 2007. While angiomatoid fibrous histiocytoma (AFH) is also reported to harbor EWSR1 translocations (20, 21), cases of AFH were only rarely reported in SEER (n=4) and therefore AFH was not further analyzed in this study. SEER classifies race into 28 mutually exclusive groups by using information from the medical record. SEER further classifies race into the major categories: “White”; “Black”; and “Others”, with the latter group including people of American Indian/Alaskan native and Asian/Pacific Islander ancestry. An additional race category includes “other unspecified” cases.

The age-adjusted annual incidence rates for several of these tumors differed according to race. Table 2 compares the incidence in the African-American population with the incidence in the white population. As expected, the most striking difference in incidence between white and African-American populations was noted in ES. The age-adjusted annual incidence of ES was 1.6 cases/1,000,000 in the white population compared to 0.2 cases/1,000,000 in the African-American population, yielding an incidence rate ratio of 0.12 (95% confidence interval 0.08 – 0.20; p < 0.001). DSRCT showed the opposite pattern, with a higher age-adjusted annual incidence rate in the African-American population (0.3 cases/1,000,000) compared to the white population (0.1 cases/1,000,000 yielding an incidence rate ratio of 3.0 (95% confidence interval 1.62 – 5.49; p < 0.001). MLPS was less common in the African-American population (age-adjusted annual incidence rate of 1.4 cases/1,000,000) compared to the white population (age-adjusted annual incidence rate of 1.6 cases/1,000,000), though this difference was not statistically significant (incidence rate ratio of 0.83; 95% confidence interval 0.66 – 1.03; p-value = 0.1). EMC, CCS and ME had comparable age-adjusted annual incidence rates that did not differ significantly between white and African-American populations.

For various cancer histologies, race related incidence differences have been demonstrated (24-26). One of the few risk factors for ES is race, even among people that have emigrated from their continents of origin (12, 13). This finding suggests a genetic component of this disease. In addition, this pattern raises the possibility that people of European ancestry have an overall higher propensity to undergo somatic translocation at the EWSR1 locus compared to people of African or Asian ancestry. The contrasting pattern of incidence by race between ES and DSRCT argues strongly against this possibility. Our analyses indicate that ES is 8 times more likely to occur in the white population compared to African-Americans and 1.9 times more likely to occur in the white population compared to Asian-Americans and Native Americans. The opposite was demonstrated for DSRCT, which is 3 times more likely to occur among African-Americans compared to whites. EWSR1 translocations are present in a very high percentage of both of these tumors (1, 10). Nevertheless, these tumors show opposite incidence rate ratios between white and African-American populations. The current findings suggest that differential propensity to translocation at the EWSR1 locus may not be responsible for the differential incidence of these tumors between racial groups. However, it is important to note that the specific breakpoints in the EWSR1 gene may differ between ES and DSRCT (1, 10). Even among tumors of the same histology, the specific breakpoints or fusion partners may differ by race, which could not be evaluated in the current study. As such, it therefore remains possible that genetic differences at specific sites within the EWSR1 gene may vary by race and mediate the differences observed in the current study.

The main strength of the use of the SEER database is the high number of analyzed mesenchymal tumor cases, which are rarely diagnosed. As with other retrospective population-based studies, this analysis comes with major limitations. First, race and tumor histology could not be independently confirmed. Second, data regarding potential environmental factors that might influence the observed differences are not available in SEER. Finally, information about genetic alterations of the tumor is not available in SEER. Instead, the tumor histology provided by SEER was viewed as a proxy for the presence of an EWSR1 translocation. This assumption may be appropriate for tumors such as ES and DSRCT that show nearly universal EWSR1 translocation (1, 10). In contrast, this assumption may be less appropriate for ME and particularly MLPS, which harbor EWSR1 gene rearrangements in only in a minority of cases (2, 3, 8, 9). ME and MLPS were included in the current analysis to provide a complete evaluation of the role of race in tumors reported to be associated with EWSR1 translocation. Despite the low frequency of EWSR1 translocation in MLPS, our findings of differences in incidence according to race should prompt further investigations into their genetic epidemiology.