Prostate Cancer Risk in South African Men
Prof Riana Bornman
Title of the project
Prostate cancer risk in South African men.
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.
We will address both biological relevance and generate data with minimal European genetic diversity within men of African descent.
Although preliminary, our results suggest that further validation and investigation into the potential implications for elevated tumor mutational burden and tumor-initiating mutations in clinically unfavorable prostate cancer can improve patient outcomes in Africa. Metagenomic analysis reveals a rich bacterial content in high-risk prostate tumors from African men (Feng et al.2019).
Inflammation is a hallmark of prostate cancer (PCa), yet no pathogenic agent has been identified. We hypothesized that pathogenic microbes may be contributing, at least in part, to high‐risk PCa presentation within Africa and in turn the observed ethnic disparity. We performed metagenomic analysis of host‐derived whole genome sequencing data to determine the microbial content within prostate tumor tissue from 22 men. What is unique about this study is that patients were separated by ethnicity, African vs European, and environments, Africa vs Australia.
We identified 23 common bacterial genera between the African, Australian, and Chinese prostate tumor samples, while nonbacterial microbes were notably absent. While the most abundant genera across all samples included: Escherichia, Propionibacterium, and Pseudomonas, the core prostate tumor microbiota was enriched for Proteobacteria. We observed a significant increase in the richness of the bacterial communities within the African vs Australian samples (t = 4.6‐5.5; P = .0004‐.001), largely driven by eight predominant genera. Considering core human gut microbiota, African prostate tissue samples appear enriched for Escherichia and Acidovorax, with an abundance of Eubacterium associated with host tumor hypermutation.
Conclusions: Our study provides suggestive evidence for the presence of a core, bacteria‐rich, prostate microbiome. While unable to exclude for 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.
- Metagenomic analysis reveals a rich bacterial content in high-risk prostate tumors from African men (2019)
- TMPRSS2‐ERG fusions linked to prostate cancer racial health disparities: A focus on Africa (2019)
- Prostate cancer genomics and racial health disparity (2018)
- Whole Genome Sequencing Reveals Elevated Tumor Mutational Burden and Initiating Driver Mutations in African Men with Treatment-Naïve, High-Risk Prostate Cancer (2018)
- Prostate Cancer in Southern Africa: Does Africa Hold Untapped Potential to Add Value to the Current Understanding of a Common Disease? (2017)
- Next-generation mapping reveals novel large genomic rearrangements in prostate cancer (2017)