TMPRSS2‐ERG fusions linked to prostate cancer racial health disparities: A focus on Africa

Abstract

Background The androgen‐regulated gene TMPRSS2 to the ETS transcription factor gene ERG fusion is the most common genomic alteration acquired during prostate tumorigenesis and biased toward men of European ancestry. In contrast, African American men present with more advanced disease, yet their tumors are less likely to acquire TMPRSS2‐ERG . Data for Africa is scarce. 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. Reverse transcription polymerase chain reaction was used to screen for the TMPRSS2‐ERG fusion, while 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 tumors 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 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.

Grade groups at diagnosis in African Caribbean men with prostate cancer: Results of a comparative study

“…Indeed, ERG expression was identified to be a promising biomarker for PCa detection and prognosis . We found that the frequency of expression of ERG was lower in our African Caribbean population (26.6%) than in our Metropolitan French population (43.1%), which is similar to the literature among African descendants and Caucasians . Moreover, we found that ERG expression was associated with lower grade groups and was a negative predictor of high‐grade groups in our African Caribbean population.…”

“…Moreover, we found that ERG expression was associated with lower grade groups and was a negative predictor of high‐grade groups in our African Caribbean population. Similarly, in African descent populations, Blackburn et al found that ERG expression was related to low‐grade disease in young patients, and Taris et al demonstrated that ERG expression was associated with longer survival in patients with both localized and castration resistance PCa. ERG expression at diagnosis might give important prognostic information, as it seems to be inversely associated with aggressive PCa in African descent men.…”

“…27 We found that the frequency of expression of ERG was lower in our African Caribbean population (26.6%) than in our Metropolitan French population (43.1%), which is similar to the literature among African descendants and Caucasians. 28 Regarding environmental factors, few studies have been able to focus on chlordecone, an insecticide close to DDT, yet known to be a human carcinogen. 32 Only two solid studies have found an association between increased chlordecone plasma concentrations and the risk of PCa.…”

Cancer in Africa: Is It a Genetic or Environmental Health Problem?

“…They observed that black men have an increased risk of transformation to clinically significant cancer compared to white men. Blackburn and his colleagues (20) tried to investigate the association between the underlying genetic differences for prostate cancer with the racial variations among peoples. They reported a lower frequency for TMPRSS2-ERG fusion which is inversely associated with aggressive prostate cancer in black South Africans males compared to those from European ancestry.…”

Histone Demethylase KDM7A Regulates Androgen Receptor Activity, and Its Chemical Inhibitor TC-E 5002 Overcomes Cisplatin-Resistance in Bladder Cancer Cells

“…A possible explanation could be the autoregulatory effect of AR on its own promoter [ 37 ]. In order to measure AR activity in KDM7A knock-down cells, the expression of previously reported downstream target genes of AR was screened using RT-qPCR [ 38 , 39 , 40 , 41 , 42 , 43 ]. The relative mRNA levels of these genes, compared with those of LNCaP, are listed in Supplemental Figure S1C .…”