rs10090154

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.

A meta-analysis of 78 case-control studies (73,996 cases, 96,741 controls) found that the rs6983267 polymorphism on chromosome 8q24 was significantly associated with increased cancer risk across all genetic models (dominant: OR=1.19, 95% CI=1.13-1.26; recessive: OR=1.19, 95% CI=1.14-1.25; homozygous: OR=1.31, 95% CI=1.23-1.40). Stratified analyses showed significant associations for colorectal cancer, prostate cancer, and thyroid cancer in Caucasians, and lung cancer in Asians.

Meta-analysis of 78 case-control studies (73,996 cases, 96,741 controls, 170,737 total subjects) examining the association between 8q24 rs6983267 G/T polymorphism and cancer susceptibility. The G risk allele was significantly associated with increased cancer risk across all genetic models (dominant: OR=1.19, 95%CI=1.13-1.26; recessive: OR=1.19, 95%CI=1.14-1.25; homozygous: OR=1.31, 95%CI=1.23-1.40). Significant associations were found for colorectal cancer, prostate cancer, thyroid cancer, and lung cancer in ethnicity-stratified analyses.

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 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 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.

Systematic literature review of 22 GWAS studies identifying 53 SNPs in 29 genomic loci associated with aggressive and progressive prostate cancer, particularly in low-grade disease. Functional analysis of 21 SNPs revealed involvement in the MYC/POU5F1B pathway (rs1447295, rs6983267, rs4242382), androgen receptor pathway (rs17021918, rs10486567, rs7679673, rs2939244), and PSA/KLK3 biomarkers (rs2735839, rs10993994). SNPs were integrated with somatic copy number aberration data, with 17 SNPs found in regions of recurrent CNAs predictive of progression; notably, rs1447295 and 7 other SNPs cluster in 8q24 gain regions harboring MYC.

This case-control study of 481 Japanese colorectal cancer patients and 962 controls found that the 8q24 variant rs6983267 is significantly associated with increased colorectal cancer risk (allelic OR = 1.22, 95% CI 1.04-1.44, p = 0.014), consistent with prior GWAS findings in other populations. The association remained significant after adjustment for lifestyle factors including smoking, alcohol consumption, folate intake, and BMI (adjusted OR = 1.25). The variant rs10090154 in the same locus did not show significant association.

This systematic review identified 53 unique SNPs in 29 genomic loci associated with aggressive prostate cancer progression and poor outcomes from GWAS studies. Functional studies implicated 21 SNPs as modulating the androgen receptor pathway, MYC oncogene, and PSA-related genes, with rs1447295 and rs10993994 being replicated across multiple populations and associated with unfavorable pathological features in low-grade prostate cancer.

This comprehensive resequence analysis of a 136 kb region of chromosome 8q24 (chr8: 128,473,000-128,609,802) using 454 next-generation sequencing identified 442 novel SNPs and characterized the complete catalog of common variation across regions previously associated with prostate and colorectal cancer risk by GWAS. The study identified 780 common SNPs, with 454 having MAF ≥5%, and determined that 114 tag SNPs are necessary to comprehensively tag the region (r² > 0.8), providing important resources for fine-mapping association signals marked by rs6983267 and rs1447295.

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.