Clinical presentation of prostate cancer in black South Africans

Abstract

Background: Compared with White Americans, Black American men are at a significant increased risk of presenting with prostate cancer (PCa) and associated mortality, suggesting a link to African-ancestry. However, PCa status within Africa is largely unknown. We address the clinical presentation of PCa within Black South African men.

Methods: Over 1,000 participants with or without PCa have enrolled in the Southern African Prostate Cancer Study (SAPCS). Using genome-wide profiling we establish a unique within Africa population substructure. Adjusting for age, clinical variables were assessed, compared against Black Americans and between rural and urban localities while addressing potential socio-demographic confounders.

Results: We report a significant difference in the distribution of prostate specific antigen (PSA) levels skewed towards higher PSA levels in the PCa cases (83.0% present with a PSA ≥ 20 µg/L; median PSA = 98.8 µg/L) relative to men with no detectable PCa (18.5% present with a PSA ≥ 20 µg/L; median PSA = 9.1 µg/L). Compared with Black Americans, Black South Africans presented with significantly more aggressive disease defined by Gleason score >7 (17% and 36%, respectively) and PSA ≥ 20 µg/L (17.2% and 83.2%, respectively). We report exasperated disease aggression defined by Gleason score >7 (P = 0.0042) and poorly differentiated tumor grade (P < 0.0001) within rural versus urban localities.

Conclusion: Black South African men present with higher PSA levels and histopathological tumor grade compared with Black Americans, which is further escalated in men from rural localities. Our data suggests that lack of PSA testing may be contributing to an aggressive PCa disease phenotype within South African men.

Keywords: African ancestry; Prostate cancer; Southern Africa; aggressive disease; clinical presentation.

Fig 1

A: Geographical localities for continental populations used in this study to define ancestral contributions including west African Mandinka (non-Bantu), Yoruba, Bamoun and Fang (western Bantu/proto-Bantu) and east African Luhya (Eastern Bantu) and (inset A) significant Southern Bantu populations from the most northerly borders of South Africa contributing to the SAPCS, specifically the Pedi, Venda, Tsonga, and Tswana. Geographical distribution of minority contributing Southern Bantu populations, specifically Swati, Ndebele, Sotho, Zulu and Xhosa, is depicted including the recruitment localities (1 to 4). Merging genome-wide genotype data for the four prominent SAPCS Southern Bantu populations (n = 36) with publically available data for west (n = 22 non-Bantu, n = 80 Western Bantu) and east African populations (n = 35 Eastern Bantu) resulted in 23,183 overlapping autosomal markers, which were used to define within Southern African and between African population substructure depicted as (B) principal component analysis including the Southern Bantu Reference Genome (ABT) [21], and (C) STRUCTURE analysis assuming three contributing populations (K = 3).

Fig 2

Clinical presentation of prostate cancer in the SAPCS cases (green) and urological controls (brown) relative to White (blue) and Black (red) populations sourced from the US-based SEER 18 Registries, with appropriate age distributions depicted as increasing color intensity with age. A: The distribution of serum PSA levels between US and SAPCS case samples for all serum PSA levels tested (PSA < 4 µg/L, PSA = 4.0–9.9 µg/L, PSA = 20–97.9 µg/L and PSA ≥ 98 µg/L). B: Gleason score (GS) distribution in SEER case samples and the SAPCS case samples for each GS < 7, GS = 7, and GS > 7.

Fig 3

Distribution of clinical prostate cancer characteristics based on collection location and defined as rural (Limpopo, orange) or urban (Gauteng, blue), for (A) serum PSA levels (including both prostate cancer cases and urological controls), (B) Gleason score, and (C) tumor grade.