Table 1. Functional information of 21 risk alleles identified to be associated with aggressive PCa.
| SNP | Location | Location of SNP – gene/Intergenic | Nearest coding gene/gene effected | Potential SNP function |
|---|---|---|---|---|
| rs13385191 | 2p24.1 | intron LDAH | LDAH | down-regulates expression of LDAH – which is down-regulated in PCa and further reduced in metastatic prostate tumors versus primary prostate tumors [61] |
| rs2660753 | 3p12.1 | Intergenic | VGLL3/CHMP2B/POU1F1 | SNP associated with the expression of VGLL3/CHMP2B/POU1F1 [58] |
| rs17021918 | 4q22 | intron PDLIM5 | BMPR1B | eQTL shows associated with (or fine mapped significantly with expression of) BMPR1B which is AR regulated [53] |
| rs7679673 | 4q24 | Intergenic | TET2 | significantly reduced TET2 expression, a predictor of disease progression and poor overall survival as binds to the androgen receptor [42] |
| rs2939244 | 5q14.3 | Intergenic | ARRDC3/LUCAT1 | variation in androgen receptor-binding site gene ARRDC3 affects prostate cancer specific mortality [56] |
| rs9364554 | 6q25.3 | intron SLC22A3 | SLC22A3 | functional studies associate this risk allele with decreased SLC22A3 transcript abundance [59] |
| rs10486567 | 7p15.2 | intron JAZF1 | JAZF1 | affects both NKX3-1 and FOXA-AR motifs in JAZF1. SNP results in a 39% increase in basal activity and a 28% fold-increase in androgen stimulated enhancer activity [59] |
| rs6465657 | 7q21.3 | intron LMTK2 | LMTK2 | effects LMTK2 expression between benign (n = 39) and malignant tissues (n = 21) (P = 0.002) [60] |
| rs6983267 | 8q24.21 | intron LOC727677/CASC8 | POU5F1B/MYC | long-range interaction with MYC in colorectal cancer [48] |
| rs1447295 | 8q24.21 | intron CASC8/LOC727677 | POU5F1B/MYC | interferes with both MYC and POU5F1B's activities through cell proliferation studies in LNCaP and C4-2B PCa cell lines [50] |
| rs4242382 | 8q24.21 | intergenic | POU5F1B/MYC | implicated in the expression of MYC and POU5F1B [50] |
| rs1571801 | 9q33.2 | intron DAP2IP | DAB2IP | *decrease in DAB2IP expression induces metastatic prostate cancer in a tumour mouse model [67] and chemoresistance in human prostate cancer cell lines [68] |
| rs10993994 | 10q11.23 | intron PARG/ TIMM23B | MSMB | associated with MSMB [57] |
| rs10896449 | 11q13.3 | intergenic | MYEOV/DUSP6 | interacts with DUSP6 [62], which promotes invasion and proliferation [63] |
| rs11568818 | 11q22.2 | intergenic | MMP-7 | associated with increased MMP7 expression [65], which mediates IL-17's function in promoting prostate carcinogenesis in mice [66] |
| rs9508016 | 13q12.2 | intron FLT1 | FLT1 | *increased FLT1 expression in prostate cancer [69] |
| rs11649743 | 17q12 | intron HNF1B | HNF1B | potentially increases HNF1B gene expression [64] |
| rs62113212 | 19q13.33 | intron KLK3 | KLK3/KLK2 | *gene encodes PSA |
| rs266870 | 19q13.33 | intron LOC105372441 | KLK3 | *gene encodes PSA |
| rs1058205 | 19q13.33 | exon KLK3 | KLK3 | *gene encodes PSA |
| rs2735839 | 19q13.33 | intergenic | KLK3 | modulates PSA levels [39] |
List of risk alleles associated with aggressive PCa, their respective chromosome, cytoband, and the location of each within either a gene or in an intergenic region as well as the gene they affect. Previously reported functional studies have been included to support these risk alleles in the role they play in aggressive PCa.
*not shown to directly affect gene expression.