Race disparities in Wilms tumor incidence and biology

Abstract

Background: Wilms tumor (WT) is thought to arise in children of Black African ancestry with greater frequency than in Whites. To clarify the biological basis for race disparities in WT, we first verified that Black children residing in Tennessee have an increased incidence of WT, and second, established molecular profiles in WT that are specific to race.

Materials and methods: To assess race disparities in WT epidemiology, the Tennessee Cancer Registry (TCR) was queried for all in-state patients less than 20 y of age and registered between 1999 and 2008. To explore race disparities in WT biology, six Black and four White WT specimens acquired in Tennessee were analyzed using imaging mass spectrometry (IMS).

Results: TCR data show that Black children are over-represented among WT patients (29%) relative to all other childhood cancers (18.5%; P = 0.01). WT ranked the fifth most common cancer diagnosis among Blacks, but ninth among Whites. The diagnosis of WT occurred 79% more frequently among Blacks (n = 28) than Whites (n = 69; P = 0.01), and proportionally more Blacks tended to present with distant disease. Although overall survival from WT was not statistically different between Blacks (92.9%) and Whites (94.0%), Black males showed the lowest survival (85%; P = 0.21). IMS analysis identified peptide spectra from both WT blastema and stroma that independently classify specimens according to race with greater than 80% accuracy.

Conclusions: In Tennessee, Black children appear more susceptible than Whites to develop WT. Race-specific molecular profiles can be determined that may help to clarify pathways of Wilms tumorigenesis and the biological basis for race disparities in WT incidence and biology.

Figure 1

Hematoxylin and eosin staining of a representative Wilms tumor specimen. (A) Cellular compartments of blastema (teal) and tumor stroma (pink) are marked for IMS analysis. (B) Higher power image of marked histologic regions within rectangle in (A).

Figure 2

Unsupervised clustering of all peptide spectra from (A) blastema and (B) stroma is able to classify Wilms tumor specimens according to race (B = black and W = white patient tumor specimens). The asterisks (*) in (A) indicate the only patient whose tumor specimens did not cluster immediately next to one another.

Figure 3

Example of a principal component analysis of peptide peaks within (A) blastema and (B) stroma that discriminate Wilms tumor specimens according to race.

Figure 4

Peptide identification and sequencing detects proteins that appear differentially expressed in Wilms tumor according to race. (A) sequencing of ACTG1. (B) individual ions scores > 47 indicate identity, p<0.05).