rs4242382

Developed a multi-state genetic variant-based Markov model for personalized prostate cancer risk stratification using Finnish population data. The model incorporates three primary SNPs (rs4242382 OR=1.75, rs138213197 OR=3.60, rs200331695 OR=6.0) and an extended panel of genetic variants to predict 10-year PCa risk ranging from 43% in the top 5% risk group to 11% in the bottom 60%, with recommendations for age-optimized screening (47 years for highest risk vs 55+ years for average/low risk) and risk-adapted interscreening intervals (< 1 year to 6+ years).

This case-control study evaluated 157 tag SNPs in the 8q24 chromosomal region in relation to papillary thyroid cancer (PTC) risk using 344 PTC cases and 452 controls. While previously cancer-associated SNPs (rs1562430, rs1447295, rs6983267) showed no significant association with PTC, one SNP (rs4733616, P=0.003) and 12 others showed uncorrected P<0.05 associations; however, none remained significant after false discovery rate correction, suggesting no strong association between 8q24 variants and sporadic PTC risk.

Analysis of 20 GWAS-identified prostate cancer susceptibility SNPs in 601 patients treated with androgen-deprivation therapy (ADT) found that rs16901979 at 8q24 was significantly associated with prostate cancer-specific mortality (HR = 0.63, 95% CI 0.45-0.87, p = 0.005) and rs7931342 at 11q13 was associated with mortality (HR = 0.65, 95% CI 0.43-0.98, p = 0.038). These variants may help predict survival outcomes in prostate cancer patients undergoing ADT treatment.

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.

A case-control study of 489 prostate cancer cases and 427 controls in a New Zealand Caucasian population examined 15 chromosome 8q24 SNPs. Four SNPs showed statistically significant associations with prostate cancer risk: rs10086908 (T allele, OR=1.64), rs16901979 (A allele, OR=2.58), rs1447295 (A allele, OR=1.70), and rs4242382 (A allele, OR=1.60). A weighted genetic risk score based on all 15 SNPs was significantly associated with prostate cancer risk (OR=1.10), with smoking contributing additional risk.

This GWAS replication study evaluated 800 SNPs in African American (n=417) and European American (n=455) prostate cancer cases versus controls (n=925 AA, n=1,687 EA) from the NC-LA Prostate Cancer Project. Of 32 European-based GWAS SNPs, 13 were significant at P<0.05 in European Americans and 4 in African Americans (rs6983267, rs7017300, rs1859962, rs6501455). Two additional SNPs reached study-wide significance: rs1472606 (OR=1.43 in EA) and rs9351265 (OR=1.48 in AA). The study confirms a large proportion of cancer-associated regions from European GWAS but shows limited predictive value (AUC=0.60 in EA, 0.56 in AA) for clinical screening.

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 comprehensive review examines genetic association studies on prostate cancer, discussing GWASs that have identified over 75 variants associated with PCa risk (as of February 2016), with major susceptibility regions at 8q24, 17q12, 17q24, 10q11, and 19q13. The paper also reviews candidate gene-based approaches targeting genes involved in androgen signaling, carcinogen metabolism, DNA repair, vitamin D signaling, inflammation, angiogenesis, and cellular adhesion, as well as regulatory RNA genes.

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.

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 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 Finnish family-based study analyzed gene-gene interactions between rs4242382 (8q24) and rs10486567 (7p15.2) in 947 subjects from 76 families with 228 prostate cancer cases. The risk allele A at rs4242382 showed OR=1.14 (95% CI 1.08-1.19) and rs10486567 showed OR=1.06 (95% CI 1.01-1.11) with a significant multiplicative gene-gene interaction (P<0.0001), suggesting synergistic epistasis for familial multiple prostate cancer, particularly in non-aggressive disease.

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.