rs13254738

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.

This case-only study of 2,147 men (1,060 African Americans, 1,087 European Americans) examined whether GWAS-identified prostate cancer susceptibility SNPs are associated with disease aggressiveness. Four GWAS replication SNPs (rs2660753, rs13254738, rs10090154, rs2735839) and 7 flanking SNPs showed significant association (P<0.05) with prostate cancer aggressiveness across 3 genomic regions (3p12, 8q24, and 19q13). The KLK3 SNPs were notably associated with PSA levels in African Americans (p<0.001) and Gleason score in both populations, though associations were not consistent across racial groups.

This study examined 10 chromosome 8q24 SNPs in 1,157 men (308 prostate cancer cases, 469 controls from West Africa, and additional Caribbean and population samples) to determine the prevalence and risk magnitude of 8q24 variants in populations of African descent. The study replicated associations between prostate cancer risk and rs6983561 (OR=0.6, P=0.03), rs16901979 (OR=1.6, P=0.03), and rs7008482 (OR=2.3) in West African men, with no significant heterogeneity of effects across African descent populations.

Case-control study of 127 African American prostate cancer cases and 345 controls from the Flint Men's Health Study examining 24 SNPs previously associated with prostate cancer in European populations. Found nominal evidence (P<0.05) for association with three 8q24 SNPs (rs6983561 OR=1.55, rs16901979 OR=1.60, rs7000448 OR=1.41) and two 10q11 SNPs (rs7904463, rs10740051 OR=0.51), replicating 8q24 findings in African Americans and providing first evidence for MSMB region association in this population.

This methods paper presents a novel retrospective likelihood approach for estimating genotype relative risks from ascertained pedigrees, which adjusts for ascertainment bias by conditioning on the phenotypes of all pedigree members. The authors apply this method to 28 previously reported prostate cancer SNPs in Mayo Clinic pedigree data (469 affected men) and case-control samples (661 cases, 518 controls), demonstrating that relative risk estimates from pedigrees are consistent with odds ratios from case-control studies.

This population-based case-control study evaluated 17 prostate cancer susceptibility loci identified in European GWAS populations in Chinese men (288 cases, 155 controls from Shanghai). Two of 17 loci on chromosome 8q24 showed significant associations with prostate cancer risk (rs1016343: OR=2.07, P=9.4×10⁻⁴; rs10090154: OR=2.07, P=0.002). Multiple additional SNPs at 8q24 regions 1 and 2 were also significantly associated with prostate cancer risk, while region 3 SNPs showed mostly null associations. Results suggest that prostate cancer risk variants identified in European populations are also relevant for Chinese men.

This case-control study investigated 15 SNPs at the 8q24 locus for association with testicular germ cell tumors (TGCT) using 568 cases and 680 controls from the STEED military study. Overall, no significant associations were found between 8q24 SNPs and TGCT risk. However, nonseminomas showed three tentative associations: rs6470494 (OR=1.68 for GG genotype, p=0.04), rs13254738 (OR=1.62 for TT genotype, p=0.07), and an inverse association with rs10505476 (OR=0.67 for CT genotype, p=0.04).

Family-based association study of 1,015 non-Hispanic white men from 403 familial and early-onset prostate cancer families examining chromosome 8q24 markers. rs6983561 (minor 'C' allele, OR=2.26) and rs6983267 (major 'G' allele, OR=1.30) showed significant associations with prostate cancer risk. rs6983561 was specifically associated with early-onset disease (age <50, p=0.03) with OR=4.69, while rs6983267 was associated with clinically aggressive disease (p=0.007) with OR=1.90.