rs7210100

This case-control study examined the association between West African ancestry (WAA) and prostate cancer (PCa) risk and aggressiveness in 291 Puerto Rican (PR) and 200 African American (AA) cases versus 133 PR and 207 AA controls. The SNP rs7824364 at chromosome 8q24 was significantly associated with PCa in both populations (p<0.0001 for AA, p=0.0001 for PR), with 82% of AA cases and 41% of PR cases carrying 1-2 risk alleles. Among PR men, those with the rs7824364 risk allele showed elevated WAA (39% versus 29%, p=0.034). No direct association between WAA and PCa aggressiveness was found.

This study integrated ChIP-seq analysis of androgen receptor-binding sites in prostate cancer cells with GWAS data and found that rs11891426:T>G in the melanophilin gene (MLPH) lies within a functional AR-binding motif, with the risk G allele attenuating transcriptional activity. Expression analysis showed MLPH was significantly lower in tumors carrying the G allele, suggesting a tumor-suppressive role weakened by this functional variant.

Genome-wide association study of 474 prostate cancer cases and 458 controls from West African men identified a novel prostate cancer susceptibility locus at 10p14 marked by rs7918885 (p=1.29×10⁻⁷), localized to an intron of the lncRNA gene RP11-543F8.2. A stratified analysis by Gleason score revealed additional associations including rs34575154 in PCDHA1 at 5q31.3 (p=3.66×10⁻⁸) for high-grade disease and rs985081 at Xq28 (p=8.66×10⁻⁹) for low-grade disease. Validation in the African Ancestry Prostate Cancer GWAS Consortium showed limited replication, with only rs2993385 at 10p14 reaching nominal significance (p<0.05), highlighting population-specific genetic architecture.