Prostate Cancer Risk in South African Men
Prof Riana Bornman
Title of the project
Prostate cancer risk in South African men.
PCa 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 PCa (and at a younger age) and 2.5 times more likely to die from PCa compared with European-Americans. The most significant risk factors for PCa namely older age, family history of PCa 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 PCa 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 PCa development. There is a definable genetic pathway from PIA to high-grade prostatic intraepithelial neoplasia (HGPIN) and to PCa. Epidemiological data supports associations between PCa risk, prostatitis and sexually transmitted infections (STIs); additional suggestive risks were increased number of sexual partners, a decreased risk associated with 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 PCa, against an inherited genetic profile of the host inflammatory network.
Aim 1: Increase number of sampling sites: We included subjects recruited from Pretoria Urology Hospital (PUH), Kalafong Hospital and Tshilidzini Hospital, Thohoyandou to increase the diversity of men with PCa in central and northern SA. We collected blood samples, questionnaire data and anthropometric measurements.
Aim 2: Biopsy tissue for possible bacterial drivers: We also collected biopsy samples from men with prostate disease for histology and extracted DNA for metagenomic analyses to identify bacterial infection. This is the first study to directly explore bacterial infection and PCa within SA men.
Aim 3: Genomic studies: Genome-wide association studies (GWAS) will be used to interrogate the coding regions of the human genome, with specific focus on inflammatory gene networks, to identify predisposing events in SA men. Using this approach we will address both biological relevance and generate data with minimal European genetic diversity within men of African descent.