African KhoeSan ancestry linked to high-risk prostate cancer.

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 (P-value?= 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

SUBMITTER: Petersen DC 

PROVIDER: S-EPMC6549381 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature