Linking African ancestral substructure to prostate cancer health disparities

Abstract

Prostate cancer (PCa) is a significant health burden in Sub-Saharan Africa, with mortality rates loosely linked to African ancestry. Yet studies aimed at identifying contributing risk factors are lacking within the continent and as such exclude for significant ancestral diversity. Here, we investigate a series of epidemiological demographic and lifestyle risk factors for 1387 men recruited as part of the multi-ethnic Southern African Prostate Cancer Study (SAPCS). We found poverty to be a decisive factor for disease grade and age at diagnosis, with other notably significant PCa associated risk factors including sexually transmitted diseases, erectile dysfunction, gynaecomastia, and vertex or complete pattern balding. Aligned with African American data, Black ethnicity showed significant risk for PCa diagnosis (OR = 1.44, 95% CI 1.05–2.00), and aggressive disease presentation (ISUP ≥ 4: OR = 2.25, 95% CI 1.49–3.40). New to this study, we demonstrate African ancestral population substructure associated PCa disparity, observing increased risk for advanced disease for the southern African Tsonga people (ISUP ≥ 4: OR = 3.43, 95% CI 1.62–7.27). Conversely, South African Coloured were less likely to be diagnosed with aggressive disease overall (ISUP ≥ 3: OR = 0.38, 95% 0.17–0.85). Understanding the basis for PCa health disparities calls for African inclusion, however, lack of available data has limited the power to begin discussions. Here, focusing on arguably the largest study of its kind for the African continent, we draw attention to the contribution of within African ancestral diversity as a contributing factor to PCa health disparities within the genetically diverse region of southern Africa.

Associating serum testosterone levels with African ancestral prostate cancer health disparities

“…Based on genetic ancestry pro ling using 33,410 linkage disequilibrium pruned single nucleotide polymorphisms, we have demonstrated that men contributing to the SAPCS and self-identifying as Southern Bantu or Black South African are genetically distinct from west, east and central African populations and in turn also African Americans, with regional within SSA population substructure separation occurring prior to European-Asian population distinction [9]. Additionally, further interrogation of genetic substructure within the SAPCS we identi ed Southern Bantu or Guthrie Zone S linguistically-driven ancestral substructure [44]. Accordingly, while the patterns of testosterone expression across diverse populations in SSA remain to be determined and in turn the impact on PCa biology and associated health disparity, studies will need to consider and de ne the deep genetic and in turn biological diversity across the region.…”

Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men

“…We note that the study sites analyzed here contain individuals from a wide range of sociolinguistic groups and genetic ancestries, and there may substantial heterogeneity in the genetic architecture of MPB and other complex traits within Africa. 62,63 Going forward, there is clear need to conduct additional studies of diverse African populations (including functional genomics experiments to infer molecular mechanisms that are due to private alleles). Because early-onset MPB is indicative of the levels of sex hormones, 64 future studies combining baldness phenotypes with genetic data may be informative about the risks of prostate cancer and other hormonal diseases.…”