A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

ABSTRACT

BACKGROUND: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. METHODS: SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. RESULTS: The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. CONCLUSIONS: This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.