Table 1.
First author, year [ref.] |
Gene(s)/loci investigated | N | Endpoint | Significant SNPs | Conclusion |
---|---|---|---|---|---|
Xu (2009) [35] | 8q24, 17q12, 3p12, 7p15, 7q21, 9q33, 10q11, 11q13, 17q24, 22q13, Xp11 | 4674, 2329 | PCa risk prediction | — | A risk prediction model, based on the number of risk alleles of 14 SNPs and family history, can predict a patients' absolute PCa risk. |
| |||||
Sun (2011) [36] | — | 4621 | PCa risk prediction | rs16901979, rs6983267, rs1447295, rs4430796, rs1855962, rs2660753, rs10486567, rs10993994, rs10896449, rs5945619, rs1465618, rs721048, rs12621278, rs10934853, rs17021918, rs7679673, rs9364554, rs2928679, rs1512268, rs16902094, rs920861, rs4962416, rs7127900, rs12418451, rs8102476, rs2735839, rs5759167 | Genetic risk prediction models are interesting to identify a subset of high-risk men at early, curable stage |
| |||||
Salinas (2009) [33] | 17q12, 17q24.3, 8q24 | 2574 | PCa risk prediction | rs4430796, rs1859962, rs6983561, rs6983267, rs1447295 | Genotyping for five SNPs plus family history is associated with a significant elevation in risk for prostate cancer. They do not improve prediction models for assessing who is at risk of getting or dying from the disease |
| |||||
Lindström (2012) [37] | EHBP1, THADA, ITGA6, EEFSEC, PDLIM5, TET2, SLC22A3, JAZF1, LMTK2, NKX3-1, SLC25A37, CPNE3, CNGB3, MSMB, CTBP2, TCF2, KLK3, BIK, NUDT11 | 15161 | PCa risk prediction | rs721048, rs1465618, rs12621278, rs2660753, rs4857841, rs17021918, rs12500426, rs7679673, rs9364554, rs10486567, rs6465657, rs6465657, rs1512268, rs2928679, rs4961199, rs1016343, rs7841060, rs16901979, rs620861, rs6983267, rs1447295, rs4242382, rs7837688, rs16902094, rs1571801, rs10993994, rs4962416, rs7127900, rs12418451, rs7931342, rs10896449, rs11649743, rs4430796, rs7501939, rs1859962, rs266849, rs2735839, rs5759167, rs5945572, rs5945619 |
Incorporating genetic information and family history in prostate cancer risk models can be useful for identifying younger men that might benefit from prostate-specific antigen screening |
| |||||
Macinnis (2011) [38] | — | 2885 | PCa risk prediction | rs721048, rs1465618, rs12621278, rs2660753, rs17021918, rs12500426, rs7679673, rs9364554, rs10486567, rs6465657, rs10505483, rs6983267, rs1447295, rs2928679, rs1512268, rs10086908, rs620861, rs10993994, rs4962416, rs7931342, rs7127900, rs4430796, rs1859962, rs2735839, rs5759167, rs5945619 | The authors developed a risk prediction algorithm for familial prostate cancer, taking into account genotyping of 26 SNPs and family history. The algorithm can be used on pedigrees of an arbitrary size or structure |
| |||||
Zheng (2009) [32] | 3p12, 7q15, 7q21, 8q24, 9q33, 10q11, 10q13, 17q12, 17q24.3, Xp11 | 4674 | PCa risk prediction | rs2660753, rs10486567, rs6465657, rs16901979, rs6983267, rs1447295, rs1571801, rs10993994, rs10896449, rs4430796, rs1859962, rs5945619C | The predictive performance for prostate cancer using these genetic variants, family history, and age is similar to that of PSA levels |
| |||||
Loeb (2009) [48] | — | 1806 | Personalized PSA testing | rs10993994, rs2735839, rs2659056 | Genotype influences the risk of prostate cancer per unit increase in prostate-specific antigen. Combined use could improve prostate specific antigen test performance |
| |||||
Helfand (2013) [49] | — | 964 | Personalized PSA testing | rs2736098, rs10788160, rs11067228, rs17632542 | Genotyping can be used to adjust a man's measured prostate-specific antigen concentration and potentially delay or prevent unnecessary prostate biopsies |
| |||||
Klein (2012) [40] | JAZF1, MYC, MSMB, NCOA4, IGF2, INS, TH, TPCN2, MYEOV, HNF1B, DPF1, PPP1R14A, SPINT2, KLK3, TTLL1, BIK, NUDT11 | 3772 | PCa risk prediction | rs10486567, rs11228565, rs17632542, rs5759167 | Prostate cancer risk prediction with SNPs alone is less accurate than with PSA at baseline, with no benefit from combining SNPs with PSA |
| |||||
Nam (2009) [41] | 17q12, 17q24.3, 8q24, ERG, HOGG1-326, KLK2, TNF, 9p22, HPC1, ETV1 | 3004 | Early detection | rs1447295, rs1859962, rs1800629, rs2348763 | When incorporated into a nomogram, genotype status contributed more significantly than PSA. The positive predictive value of the PSA test ranged from 42% to 94% depending on the number of variant genotypes carried |
| |||||
Aly (2011) [42] | THADA, EHBP1, ITGA6, EEFSEC, PDLIM5, FLJ20032, SLC22A3, JAZF1, LMTK2, NKX3-1, MSMB, CTBP2, HNF1B, PPP1R14A, KLK3, TNRC6B, BIK, NUDT11, 8q24.21, 11q15.5, 11q13.2, 17q24.3 | 5241 | PCa risk prediction | rs721048, rs12621278, rs7679673, rs10086908, rs1016343, rs13252298, rs6983561, rs16901979, rs16902094, rs6983267, rs1447295, rs10993994, rs7127900, rs10896449, rs11649743, rs4430796, rs1859962, rs8102476, rs2735839, rs5759167, rs5945619 | Using a genetic risk score, implemented in a risk-prediction model, there was a 22.7% reduction in biopsies at a cost of missing a PCa diagnosis in 3% of patients characterized as having an aggressive disease |
| |||||
Hirata (2009) [70] | P53, p21, MDM2, PTEN, GNAS1, bcl2 | 167 | BCR after RP | rs2279115 | Bcl2 promotor region −938 C/C genotype carriers more frequently show biochemical recurrence than −938 C/A + A/A carriers |
| |||||
Perez (2010) [58] | EGFR | 212 | BCR after RP | rs8844019 | Statistically significant association between the SP and prostate biochemical recurrence after radical prostatectomy |
| |||||
Morote (2010) [71] | KLK2, SULT1A1, TLR4 | 703 | BCR after RP | rs198977, rs9282861, rs11536889 | Predicting biochemical recurrence after radical prostatectomy based on clinicopathological data can be significantly improved by including patient genetic information |
| |||||
Audet-Walsh (2011) [61] | SRD5A1, SRD5A2 | 846 | BCR after RP | rs2208532, rs12470143, rs523349, rs4952197, rs518673, rs12470143 | Multiple SRD5A1 and SRD5A2 variations are associated with increased/decreased rates of BCR after RP |
| |||||
Audet-Walsh (2012) [60] | HSD17B1, HSD17B2, HSD17B3, HSD17B4, HSD17B5, HSD17B12 | 526 | BCR after RP | rs1364287, rs8059915, rs2955162, rs4243229, rs1119933, rs9934209, rs7201637, rs10739847, rs2257157, rs1810711, rs11037662, rs7928523, rs12800235, rs10838151 | Twelve SNPs distributed across HSD17B2, HSD17B3, and HSD17B12 were associated with increased risk of BCR in localized PCa after RP |
| |||||
Jaboin (2011) [67] | MMP7 | 212 | BCR after RP | rs10895304 | The A/G genotype is predictive of decreased recurrence-free survival in patients with clinically localized prostate cancer |
| |||||
Wang (2009) [68] | PCGF2 (MEL-18) | 124 | BCR after RP | rs708692 | Patients with the G/G genotype have a significantly higher rate of BCR after RP. |
| |||||
Bachmann (2011) [69] | bcl2 | 290 | BCR after RP | rs2279115 | The −938 A/A genotype carriers more frequently show biochemical recurrence than −938 C/A + C/C carriers |
| |||||
Huang (2010) [64] | CTNNB1, APC | 307 | BCR after RP | rs3846716 | There is a potential prognostic role of the GA/AA genotype of the SNP on BCR after RP. |
| |||||
Chang (2013) [65] | IGF1, IGF1R | 320 | BCR after RP | rs2946834, rs2016347 | A genetic interaction between IGF1 rs2946834 and IGF1R rs2016347 is associated with BCR after RP. |
| |||||
Borque (2013) [72] | KLK3, KLK2, SULT1A1, BGLAP | 670 | BCR after RP | rs2569733, rs198977, rs9282861, rs1800247 | A nomogram, including SNPs and clinicopathological factors, improves the preoperative prediction of early BCR after RP |
| |||||
Langsenlehner (2011) [73] | XRCC1 | 603 | RT toxicity | rs25489 | The XRCC1 Arg280His polymorphism may be protective against the development of high-grade late toxicity after radiotherapy. |
| |||||
Damaraju (2006) [77] | BRCA1, BRCA2, ESR1, XRCC1, XRCC2, XRCC3, NBN, RAD51, RAD2-52, LIG4, ATM, BCL2, TGFB1, MSH6, ERCC2, XPF, NR3C1, CYP1A1, CYP2C9, CYP2C19, CYP3A5, CYP2D6, CYP11B2, CYP17A1 | 83 | RT toxicity | rs1805386, rs1052555, rs1800716 | SNPs in LIG4, ERC22, and CYP2D6 are putative markers to predict individuals at risk for complications arising from radiation therapy |
| |||||
De Langhe (2013) [78] | TGFβ1 | 322 | RT toxicity | rs1800469, rs1982073 | Radical prostatectomy, the presence of pretreatment nocturia symptoms, and the variant alleles of TGFβ1 −509 C > T and codon 10 T > C are identified as factors involved in the development of acute radiation-induced nocturia when treated with IMRT |
| |||||
Fachal (2012) [79] | ATM, ERCC2, LIG4, MLH1, XRCC3 | 698 | RT toxicity | rs1799794 | The SNP and the mean dose received by the rectum are associated with the development of gastrointestinal toxicity after 3D-CRT. |
| |||||
Fachal (2012) [80] | TGFβ1 | 413 | RT toxicity | None | Neither of the investigated SNPs or haplotypes were found to be associated with the risk of late toxicity. |
| |||||
Popanda (2009) [81] | XRCC1, APEX1, hOGG1, XRCC2, XRCC3, NBN, XPA, ERCC1, XPC, TP53, P21, MDM2 | 405 | RT toxicity | rs25487, rs861539 | The XRCC1 Arg399Gln polymorphism is associated with an increase in risk for heterozygous individuals and for Gln carriers. For XRCC3 Thr241Met, the Met variant increases the risk in Met carriers |
| |||||
Suga (2008) [82] | SART1, ID3, EPDR1, PAH, XRCC6 | 197 | RT toxicity |
rs2276015, rs2742946, rs1376264, rs1126758, rs2267437 | Two-stage AUC-ROC curve reached a maximum of 0.86 (training set) in predicting late genitourinary morbidity |
| |||||
Cesaretti (2005) [85] | ATM | 37 | RT toxicity (Brachy) | — | There is a strong association between sequence variants in the ATM gene and erectile dysfunction/rectal bleeding |
| |||||
Cesaretti (2007) [84] | ATM | 108 | RT toxicity (Brachy) | — | The possession of SNPs in the ATM gene is associated with the development of radiation-induced proctitis after brachytherapy |
| |||||
Peters (2008) [86] | TGFβ1 | 141 | RT toxicity (Brachy) | rs1982073, rs1800469, rs1800471 | Presence of certain TGFβ1 genotypes is associated with the development of both erectile dysfunction and late rectal bleeding in patients treated with radiotherapy. |
| |||||
Pugh (2009) [87] | ATM, BRCA1, ERCC2, H2AFX, LIG4, MDC1, MRE11A, RAD50 | 41 | RT toxicity (Brachy) | rs28986317 | The high toxicity group is enriched for at least one LIG4 SNP. One SNP in MDC1 is associated with increased radiosensitivity. |
| |||||
Burri (2008) [88] | SOD2, XRCC1, XRCC3 | 135 | RT toxicity | rs25489, rs4880, rs861539 | A XRCC1 SNP is associated with erectile dysfunction. A combination of a SNP in SOD2 and XRCC3 is associated with late rectal bleeding |
| |||||
Barnett (2012) [89] | ABCA1, ALAD, APEX1, ATM, BAX, CD44, CDKN1A, DCLRE1C, EPDR1, ERCC2, ERCC4, GSTA1, GSTP1, HIF1A, IL12RB2, LIG3, LIG4, MED2L2, MAP3K7, MAT1A, MLH1, MPO, MRE11A, MSH2, NEIL3, NFE2L2, NOS3, PAH, PRKDC, PTTG1, RAD17, RAD21, RAD9A, REV3L, SART1, SH3GL1, SOD2, TGFB1, TGFB3, TP53, XPC, XRCC1, XRCC3, XRCC5, XRCC6 | 637 | RT toxicity | None | None of the previously reported associations were confirmed by this study, after adjustment for multiple comparisons. The P value distribution of the SNPs tested against overall toxicity score was not different from that expected by chance |
| |||||
Ross (2008) [97] | AKR1C1, AKR1C2, AKR1C3, AR, CYP11A1, CYP11B1, CYP17A1, CYP19A1, CYP21A2, CYP3A4, DHRS9, HSD17B3, HSD17B4, HSD3B1, HSD3B2, MAOA, SRD5A1, SRD5A2, SREBF2, UGT2B15 | 529 | ADT efficacy | rs1870050, rs1856888, rs7737181 | Three polymorphisms in separate genes are significantly associated with time to progression during ADT. |
| |||||
Teixeira (2008) [100] | EGF | 275 | ADT efficacy | rs4444903 | EGF functional polymorphism may contribute to earlier relapse in ABT patients, supporting the involvement of EGF as an alternative pathway in hormone-resistant prostatic tumors |
| |||||
Yang (2011) [101] | SLCO2B1, SLCO1B3 | 538 | ADT efficacy | rs12422149, rs1789693, rs1077858 | Three SNPs in SLCO2B1 were associated with time to progression (TTP) on ADT. Patients carrying both SLCO2B1 and SLCO1B3 genotypes, which import androgens more efficiently, exhibited a median 2-year shorter TTP on ADT |
| |||||
Teixeira (2013) [102] | TGFBR2 | 1765 | ADT efficacy | — | TGFBR2-875GG homozygous patients have an increased risk of an early relapse after ADT. Combining clinicopathological and genetic information resulted in an increased capacity to predict the risk of ADT failure |
| |||||
Kohli (2012) [103] | TRMT11, HSD17B12, PRMT3, WBSCR22, CYP3A4, PRMT2, SULT2B1, SRD5A1, AKR1D1, UGT2A1, SULT1E, HSD3B1, UGT2A3, UGT2B11, UGT2B28, CYP19A1, PRMT7, METTL2B, HSD17B3, LCMT1, UGT2B7, SRD5A2, CYP11B2, CARM1, METTL6, HSD17B1, HEMK1, CYP11B1, ESR1, UGT2B10, SERPINE1, PRMT6, HSD11B1, THBS1, SULT2A1, UGT2B4, PRMT5, PRMT8, HSD3B2, UGT1A4, ARSE, UGT1A8, UGT1A5, UGT1A10, ESR2, LCMT2, UGT1A9, AR, UGT1A6, UGT1A7, AKR1C4, STS, HSD17B8, ARSD, HSD17B2, HSD17B7, UGT1A1, UGT1A3, | 304 | ADT efficacy | rs1268121, rs6900796 | TRMT11 showed the strongest association with time to ADT failure, with two of 4 TRMT 11 tagSNPs associated with time to ADT failure. |
| |||||
Bao (2011) [104] | KIF3C, CDON, ETS1, IFI30, has-mir-423, PALLD, ACSL1, GABRA1, SYT9, ZDHHC7, MTRR | 601 | ADT efficacy | rs6728684, rs3737336, rs1045747, rs1071738, rs998754, rs4351800 |
KIF3C rs6728684, CDON rs3737336, and IFI30 rs1045747 genotypes remained as significant predictors for disease progression in multivariate models that included clinicopathologic predictors. A greater number of unfavorable genotypes were associated with a shorter time to progression and worse prostate cancer-specific survival during ADT. |
| |||||
Huang (2012) [106] | SPRED2, GNPDA2, BNC2, ZNF521, ZNF507, ALPK1, SKAP2, TACC2, SKAP1, KLHL14, NR4A2, FBXO32, AATF | 601 | ADT efficacy | rs16934641, rs3763763, rs2051778, rs3763763 | Genetic variants in BNC2, TACC2, and ALPK1 are associated with clinical outcomes after ADT, with a cumulative effect on ACM following ADT of combinations of genotypes across the two loci of interest. |
| |||||
Huang (2012) [105] | ACTN2, NR2F1, ARRDC3, XRCC6BP1, FLT1, PSMD7, SKAP1, FBXO32, FLRT3 | 601 | ADT efficacy | rs2939244, rs9508016, rs6504145, rs7830622, rs9508016 | Genetic variants in ARRDC3, FLT1, and SKAP1 are significant predictors for PCSM and genetic variants in FBXO32 and FLT1 remained significant predictors for ACM. There was a strong combined genotype effect on PCSM and ACM. |
| |||||
Huang (2012) [107] | BMP5, NCOR2, IRS2, MAP2K6, RXRA, ERG, BMPR1A | 601 | ADT efficacy | rs4862396, rs3734444, rs7986346 | Genetic variants in CASP3, BMP5, and IRS2 are associated with ACM. Genetic variation in BMP5 and IRS2 is significantly related to PCSM. Patients carrying a greater number of unfavorable genotypes at the loci of interest have a shorter time to ACM and PCSM during ADT. |
| |||||
Tsuchiya (2013) [108] | IGF-1 | 251 | Metastatic PCa outcome | — | When the sum of the risk genetic factors in each LD block was considered, patients with all the risk factors had significantly shorter cancer-specific survival than those with 0–2 risk factors. |
| |||||
Pastina (2010) [112] | CYP1B1 | 60 | Docetaxel response | rs1056836 | The polymorphism is a possible predictive marker of response and clinical outcome to docetaxel in CRPC patients. |
| |||||
Sissung (2008) [113] | CYP1B1 | 52 | Docetaxel response | rs1056836 | Individuals carrying two copies of the polymorphic variant have a poor prognosis after docetaxel-based therapies compared with individuals carrying at least one copy of the allele. |
| |||||
Sissung (2008) [114] | ABCB1 | 73 | Docetaxel response | — | Docetaxel-induced neuropathy, neutropenia grade, and overall survival could be linked to ABCB1 allelic variants (diplotypes). |
Listing all the studies being discussed. From left to right: author (ref), genes/loci tested, number of patients included in the cohort, general endpoint of the study, significant SNPs, and conclusions.