This is the first comprehensive analysis of racial differences in the incidence of mesenchymal tumors associated with EWSR1 gene translocations. The results confirm previous reports of strong racial differences in the incidence of Ewing sarcoma and provide the first description of significant racial differences in the incidence of both DSRCT and MLPS. Specifically, DSRCT was significantly more common in the African-American population compared to the white population. In addition, MLPS had a lower incidence among the American Indian/Alaskan native and Asian/Pacific Islander population compared to the white population. These findings suggest that the relationship between EWSR1 translocation and race is complex.
For various cancer histologies, race related incidence differences have been demonstrated (24
). One of the few risk factors for ES is race, even among people that have emigrated from their continents of origin (12
). 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
). 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
). 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
). 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
). 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.
Despite these limitations, the significant differences in incidence rates according to race suggest that genetic differences may underlie the pathogenesis of these tumors. However, these tumors do not appear to share common racial differences in the propensity for EWSR1 translocation. Additional study of the genetic epidemiology of these rare tumors will provide further insight into their pathogenesis.