36 The Southern African Prostate Cancer Study (SAPCS) was established in 2008, with seed funding from the Medical Research Council (MRC) of South Africa, to address the impact and aetiology of prostate cancer in Black South African men, with the inclusion of the most rural communities. After adjusting for age, we showed that Black South African men have a 2.1-fold greater risk for aggressive cancer at presentation than reported for African Americans, while within South Africa, men from Limpopo were at 1.6-fold greater risk of presenting with advanced disease than men from 7 Gauteng . As with global studies, explanations for this marked geographic/ethnic disparity could be environmental (including lifestyle or socioeconomic factors) or genetic (ancestral inheritance), or a combination of these genetic and non-genetic contributions. While no modiable risk factor has been identied for prostate cancer, family history of cancer, along with an African ancestry is one of only three veried risk factors, with prostate cancer having one of the highest heritability rates for any 8 solid tumour . The third established risk factor, an increasing age. While age is neither driven by genetics nor environment, it is notable that the regions of the world with the highest mortality rates, also report the lowest global average lifeexpectancies, which further supports research efforts focused on understanding the underlying aetiology of prostate cancer health disparities. We have previously proposed that South Africa holds till now untapped potential to address these 9 contributing factors . Ultimately, the SAPCS team has established a precision health model aimed at unravelling the biological and non-biological mechanisms behind prostate cancer health disparity. Precision health is an approach to healthcare that treats the individual, rather than the collective. It takes one’s environment, lifestyle and genetics into consideration when diagnosing, preventing and treating disease, such as prostate cancer. Today, men of African ancestry are largely treated based on data generated from men of European ancestry. Yet, we know that men of African ancestry (or from Africa) have a higher disease burden, which leaves the question if we are doing the best we can for our population. Ultimately, prostate cancer is a genetic disease. While one’s ancestral inheritance may contribute to cancer risk, non-genetic (environmental) forces leave a computationally derived signature within the growing tumour genome, providing a pattern of DNA variation as a direct consequence of 10 contributing carcinogenic inuences . In a rst-ofits-kind study for any cancer across Sub-Saharan Africa, the SAPCS team has been sequencing (generating the DNA code) for South African prostate cancer patients and their tumours and comparing these mutational signatures between geographies and ethnicities. Published recently in 11 nature , we identied African-specic oncogenic drivers and tumour burden, including novel driver 12 complexity , which proposes unmet opportunities for African-relevant options and hope for treating aggressive disease. Additionally, we describe a new African-relevant tumour genetic subgrouping and mutational signatures, which for the rst time raises the possibility that a yet unknown environmental factor may be contributing, at least in part, to aggressive prostate cancer within South Africa. Most recently, the team has combined forces with colleagues in Kenya, via the East African Prostate Cancer Study (EACPS), led by Professor Peter Ngugi (University of Nairobi), and in the Unites States, via the Chicago Prostate Cancer Study (ChiPCS), led by Professor Gail Prins (University of Illinois at Chicago), as the United State Department of Defense (DoD) funded Prostate Cancer Research Program (PCRP) Health Equity Research and Outcomes Improvement Consortium (HEROIC) awarded HEROIC Prostate Cancer Precision Health (PCaPH) Africa1K to address the contribution of genetic and non-genetic factors driving prostate cancer health disparity and reduce the impact of prostate cancer associated death for men of African ancestry (launched August 2022). Led by the words of the Arch, ‘There comes a point where we need to just stop pulling people out of the river. We need to go upstream and nd out why they are falling in’, we are going upstream. Acknowledgements The SAPCS management team (VMH, SBAM, MSRB) are forever grateful to the many study participants and their families who have over a decade been willing to participate in this research. To the many clinicians, nurses and eld workers who have made the SAPCS possible, we owe you great appreciation. A special thanks goes out to past inaugural SAPCS members, the late Professor Philip Venter, Dr Richard Monare and Dr Smit van Zyl, previously from the University of Limpopo (South Africa), whom without their enthusiasm and dedication, the SAPCS would not have been possible. We thank the Tutu family for allowing the Arch’s words to continue and for sharing so gracefully their precious husband, father and grandfather with the team and the world. We acknowledge the Cancer Association of South Africa (CANSA), who are enabling the SAPCS to bring our research to the remote communities of South Africa. Most recently, we acknowledge the National Health and Medical Research Council (NHMRC; grants APP1165762, APP2001098 and APP2010551) of Australia and the Congressionally Directed Medical Research Program (CDMRP), previously the Department of Defense (DoD), Prostate Cancer Research Program (PCRP; awards PC200390 and PC210168) of the United States, for their vision to support this important work and to bring genomic based precision health to South Africa and in turn reduce the impact of prostate cancer health disparities. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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