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Prostate Cancer Risk in South African Men

Prof Riana Bornman

Project ended 30 June 2020

Prof Riana Bornman

Title of the project

Prostate cancer risk in South African men.

Project Description

Prostate cancer globally has one of the highest ethnic-based associations for any human cancer and population-based studies showed that African-Americans are 1.7 times more likely to be diagnosed with prostate cancer (and at a younger age) and 2.5 times more likely to die from prostate cancer compared with European-Americans. The most significant risk factors for prostate cancer namely older age, family history of prostate cancer and African ancestry, suggest that both environmental and genetic factors are likely contributors to susceptibility and disease course.

Markers of chronic inflammation are significantly associated with cancer in general and with prostate cancer in particular. Infections play a critical role in cancer development and contribute to 15-20% of all human cancers worldwide, but even more within Africa (~26%). Proliferative inflammatory atrophy (PIA), possibly a result of pathogenic infection, is a common condition in the prostates of older men and may promote prostate cancer development. There is a definable genetic pathway from PIA to high-grade prostatic intraepithelial neoplasia (HGPIN) and to prostate cancer. Epidemiological data support associations between prostate cancer risk, prostatitis and sexually transmitted infections (STIs); additional suggestive risks were increased number of sexual partners, a decreased risk associated with an increased number of ejaculations (suggesting pathogen clearance), increased risk associated with a history of asthma (a chronic inflammatory disease) and the use of asthma medications, and a decreased risk associated with the use of non-steroidal anti-inflammatory drugs.

We hypothesized that bacterial pathogenic agents could be contributors to prostate cancer, against an inherited genetic profile of the host inflammatory network.

Our study provides suggestive evidence for the presence of a core, bacteria‐rich, prostate microbiome. While unable to exclude fecal contamination, the observed increased bacterial content and richness within the African vs non‐African samples, together with elevated tumor mutational burden, suggests the possibility that bacterially‐driven oncogenic transformation within the prostate microenvironment may be contributing to aggressive disease presentation in Africa.

Value of the project in the struggle against cancer

To the best of our knowledge, this is the first systematic study funded by CANSA on prostate cancer in African men. The funding allowed for questionnaire data to be collected from diverse populations presenting at different institutions in central and northern SA: at Pretoria Urology Hospital (PUH) predominantly white men were recruited, at Kalafong and George Mukhari Hospital predominantly black men, but also white and coloured men and only blacks at Tshilidzini Hospital. The data collected allows for in depth assessment of the similarities and differences in the clinical presentation at the time of prostate biopsy for prostatic disease.

The opportunity to use of the existing lines of communication in a tribal setting, allowed for first-hand experience for future planning a detailed assessment and a situational analysis of PCa awareness. This will allow for studies on how to approach men more effectively from remote rural areas when creating awareness. The finding of elevated tumor mutational burden (TMB) and initiating driver mutations in African men with treatment-naïve, high-risk prostate cancer (Jaratlerdsiri et al., 2018), raises an important possibility that an as yet unknown environmental/carcinogenic and/or genetic factors, are contributing to the increased TMB in men from Africa. This may include potential to provide an opportunity to treat aggressive disease through immunotherapy [24,25]. These findings should be confirmed by further studies, including exposure assessment of environmental chemicals.

KhoeSan ancestry linked to advanced PCa. Showing that a large majority of South African’s carry a significant percentage of KhoeSan genetic ancestry [6,11,12,15,16], together with colleagues from Stellenbosch University (South Africa), we suggest a link between percentage KhoeSan ancestry and high-risk PCa defined both by advanced pathology and/or elevated PSA levels [20]. ERG fusions are not common in the SAPCS. The androgen-regulated gene TMPRSS2 is fused to the transcription factor gene ERG in PCa from 50% of men of European ancestry. In contrast, we found this mutation to be relatively rare in men of African ancestry (13%), half that reported for African Americans [26]. We found this fusion to be associated with low-grade PCa in younger aged patients, calling for the evaluation of hormone-based therapies in men of African ancestry. The findings of this study open new hypotheses to study elucidate the development and treatment of PCa in African men, as well as to more effectively planning awareness in remote rural communities.

 Future plans for the research

We want to secure funding to study the possible role of environmental exposures to chemicals such as dichlorodiphenyl-trichloroethane (DDT) through residual spraying for malaria control in endemic regions, like in Vhembe.

Publications

Booklet 8 CANSA Detectives

Southern African Prostate Cancer Study (SAPCS)

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