African KhoeSan ancestry linked to high-risk prostate cancer

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Authors

Petersen, Desiree C.
Jaratlerdsiri, Weerachai
Van Wyk, Abraham
Chan, Eva K.F.
Fernandez, Pedro
Lyons, Ruth J.
Mutambirw, Shingai B.A.
Van der Merwe, Andre
Bates, William
Bornman, Maria S. (Riana)

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Volume Title

Publisher

BioMed Central

Abstract

BACKGROUNDS : Genetic diversity is greatest within Africa, in particular the KhoeSan click-speaking peoples of southern Africa. South African populations represent admixture fractions including differing degrees of African, African-KhoeSan and non-African genetic ancestries. Within the United States, African ancestry has been linked to prostate cancer presentation and mortality. Together with environmental contributions, genetics is a significant risk factor for high-risk prostate cancer, defined by a pathological Gleason score ≥ 8. METHODS : Using genotype array data merged with ancestry informative reference data, we investigate the contribution of African ancestral fractions to high-risk prostate cancer. Our study includes 152 South African men of African (Black) or African-admixed (Coloured) ancestries, in which 40% showed high-risk prostate cancer. RESULTS : Genetic fractions were determined for averaging an equal African to non-African genetic ancestral contribution in the Coloured; we found African ancestry to be linked to high-risk prostate cancer (P-value = 0.0477). Adjusting for age, the associated African ancestral fraction was driven by a significant KhoeSan over Bantu contribution, defined by Gleason score ≥ 8 (P-value = 0.02329) or prostate specific antigen levels ≥20 ng/ml (Pvalue = 0.03713). Additionally, we observed the mean overall KhoeSan contribution to be increased in Black patients with high-risk (11.8%) over low-risk (10.9%) disease. Linking for the first time KhoeSan ancestry to a common modern disease, namely high-risk prostate cancer, we tested in this small study the validity of using KhoeSan ancestry as a surrogate for identifying potential high-risk prostate cancer risk loci. As such, we identified four loci within chromosomal regions 2p11.2, 3p14, 8q23 and 22q13.2 (P-value = all age-adjusted < 0.01), two of which have previously been associated with high-risk prostate cancer. CONCLUSIONS : Our study suggests that ancient KhoeSan ancestry may be linked to common modern diseases, specifically those of late onset and therefore unlikely to have undergone exclusive selective pressure. As such we show within a uniquely admixed South African population a link between KhoeSan ancestry and high-risk prostate cancer, which may explain the 2-fold increase in presentation in Black South Africans compared with African Americans.

Description

Additional file 1: Table S1. Clinical classification of Coloured patients with prostate cancer.
Additional file 2: Genotyping data of 68 Black participants (PED and MAP formats).
Additional file 3: Genotyping data of 84 Coloured participants (PED and MAP formats).

Keywords

African ancestry, Prostate cancer, KhoeSan, High-risk disease, Ancestral fractions, Ancestry informative markers

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Citation

Petersen, D.C., Jaratlerdsiri, W., Van Wyk, A. et al. 2019, 'African KhoeSan ancestry linked to high-risk prostate cancer', BMC Medical Genomics, vol. 12, art. 82, pp. 1-7.