TMPRSS2-ERG fusions linked to prostate cancer racial health disparities: a focus on Africa

Background: To determine the frequency and isoform presentation of the TMPRSS2-ERG gene fusion in prostate tissue from 181 Black South Africans either with or without prostate cancer, which may explain elevated aggressive disease presentation in men of African ancestry.Methods: RNA was made available for genomic analyses from 181 prostate tissue biopsy cores from Black South African men, 94 with and 87 without pathological evidence for prostate cancer. RT-PCR was used to screen for the most frequent somatic alteration identified for primary prostate cancer, namely fusion of the androgen-regulated gene TMPRSS2 to the ETS transcription factor gene ERG. TMPRSS2-ERG fusion transcript junction coordinates and isoform frequencies, including novel gene fusions, were determined using targeted RNA sequencing.Results: Here we report a frequency of 13% for TMPRSS2-ERG in tumours from Black South Africans. Present in 12/94 positive versus 1/87 cancer negative prostate tissue cores, this suggests a 92.62% predictivity for a positive cancer diagnosis (P = 0.0031). At a frequency of almost half that reported for African Americans and roughly a quarter of that reported for men of European ancestry, acquisition of TMPRSS2-ERG appears to be inversely associated with aggressive prostate cancer. Further support was provided by linking the presence of TMPRSS2-ERG to low-grade disease in younger patients (P = 0.0466), with higher expressing distal ERG fusion junction coordinates.Conclusions: Significant health disparity in prostate cancer outcomes and mortality rates exists within the United States. While African American men are at 2.4-fold greater risk of dying from prostate cancer than European Americans, Black South African men are at a further 2.1-fold increased risk for aggressive disease presentation than African Americans. Only the second study of its kind for the African continent, we support a link between TMPRSS2-ERG status and prostate cancer racial health disparity beyond the borders of the United States. We call for urgent evaluation of androgen deprivation therapy within Africa.