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Article: How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis

TitleHow Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis
Authors
KeywordsGenetic variance
Polygenic risk score
Prostate cancer risk
Single-nucleotide polymorphism
Issue Date2023
Citation
Clinical Genitourinary Cancer, 2023, v. 21, n. 2, p. 316.e1-316.e11 How to Cite?
AbstractObjectives: Genome-wide association studies have revealed over 200 genetic susceptibility loci for prostate cancer (PCa). By combining them, polygenic risk scores (PRS) can be generated to predict risk of PCa. We summarize the published evidence and conduct meta-analyses of PRS as a predictor of PCa risk in Caucasian men. Patients and methods: Data were extracted from 59 studies, with 16 studies including 17 separate analyses used in the main meta-analysis with a total of 20,786 cases and 69,106 controls identified through a systematic search of ten databases. Random effects meta-analysis was used to obtain pooled estimates of area under the receiver-operating characteristic curve (AUC). Meta-regression was used to assess the impact of number of single-nucleotide polymorphisms (SNPs) incorporated in PRS on AUC. Heterogeneity is expressed as I2 scores. Publication bias was evaluated using funnel plots and Egger tests. Results: The ability of PRS to identify men with PCa was modest (pooled AUC 0.63, 95% CI 0.62-0.64) with moderate consistency (I2 64%). Combining PRS with clinical variables increased the pooled AUC to 0.74 (0.68-0.81). Meta-regression showed only negligible increase in AUC for adding incremental SNPs. Despite moderate heterogeneity, publication bias was not evident. Conclusion: Typically, PRS accuracy is comparable to PSA or family history with a pooled AUC value 0.63 indicating mediocre performance for PRS alone.
Persistent Identifierhttp://hdl.handle.net/10722/328887
ISSN
2023 Impact Factor: 2.3
2023 SCImago Journal Rankings: 1.056
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSiltari, Aino-
dc.contributor.authorLönnerbro, Ragnar-
dc.contributor.authorPang, Karl-
dc.contributor.authorShiranov, Kirill-
dc.contributor.authorAsiimwe, Alex-
dc.contributor.authorEvans-Axelsson, Susan-
dc.contributor.authorFranks, Billy-
dc.contributor.authorKiran, Amit-
dc.contributor.authorMurtola, Teemu J.-
dc.contributor.authorSteinbeisser, Carl-
dc.contributor.authorBjartell, Anders-
dc.contributor.authorAuvinen, Anssi-
dc.contributor.authorN'Dow, J.-
dc.contributor.authorSmith, E. J.-
dc.contributor.authorShepherd, R.-
dc.contributor.authorRibal, M.-
dc.contributor.authorMottet, N.-
dc.contributor.authorMoris, L.-
dc.contributor.authorLardas, M.-
dc.contributor.authorWillemse, P. P.-
dc.contributor.authorGandaglia, G.-
dc.contributor.authorCampi, R.-
dc.contributor.authorNicoletti, Rossella-
dc.contributor.authorGacci, M.-
dc.contributor.authorBriganti, A.-
dc.contributor.authorRatti, M. M.-
dc.contributor.authorAlleva, E.-
dc.contributor.authorLeardini, L.-
dc.contributor.authorSisca, E. S.-
dc.contributor.authorBangma, R.-
dc.contributor.authorRoobol, M.-
dc.contributor.authorRemmers, S.-
dc.contributor.authorTilki, D.-
dc.contributor.authorVisakorpi, T.-
dc.contributor.authorTalala, K.-
dc.contributor.authorTammela, T.-
dc.contributor.authorvan Hemelrijck, M.-
dc.contributor.authorBayer, K.-
dc.contributor.authorLejeune, S.-
dc.contributor.authorByrne, S.-
dc.contributor.authorFialho, L.-
dc.contributor.authorDe Meulder, P. Palaiologou B.-
dc.contributor.authorAuffray, C.-
dc.contributor.authorHijazy, A.-
dc.contributor.authorPower, S.-
dc.contributor.authorKermani, N. Zounemat-
dc.contributor.authorvan Bochove, K.-
dc.contributor.authorKalafati, M.-
dc.contributor.authorMoinat, M.-
dc.contributor.authorVoss, E.-
dc.contributor.authorHorgan, D.-
dc.contributor.authorFullwood, L.-
dc.contributor.authorHoltorf, M.-
dc.contributor.authorLancet, D.-
dc.contributor.authorBernstein, G.-
dc.contributor.authorOmar, I.-
dc.contributor.authorMaclennan, S.-
dc.contributor.authorTripathee, S.-
dc.contributor.authorWirth, M.-
dc.contributor.authorFroehner, M.-
dc.contributor.authorBrenner, B.-
dc.contributor.authorBorkowetz, A.-
dc.contributor.authorThomas, C.-
dc.contributor.authorHorn, F.-
dc.contributor.authorReiche, K.-
dc.contributor.authorKreux, M.-
dc.contributor.authorJosefsson, A.-
dc.contributor.authorTandefekt, D. Gasi-
dc.contributor.authorHugosson, J.-
dc.contributor.authorHuisman, H.-
dc.contributor.authorSchalken, J.-
dc.contributor.authorHofmacher, T.-
dc.contributor.authorLindgren, P.-
dc.contributor.authorAndersson, E.-
dc.contributor.authorFridhammar, A.-
dc.contributor.authorZong, J.-
dc.contributor.authorButler-Ransohoff, J. E.-
dc.contributor.authorHerrera, R.-
dc.contributor.authorMaass, M.-
dc.contributor.authorTorremante, P.-
dc.contributor.authorVoss, M. D.-
dc.contributor.authorDevecseri, Z.-
dc.contributor.authorAbbott, T.-
dc.contributor.authorDau, C.-
dc.contributor.authorPapineni, K.-
dc.contributor.authorSnijder, R.-
dc.contributor.authorLambrecht, M.-
dc.contributor.authorWolfinger, R.-
dc.contributor.authorRogiers, S.-
dc.contributor.authorServan, A.-
dc.contributor.authorAntoni, L.-
dc.contributor.authorPacoe, K.-
dc.contributor.authorRobinson, P.-
dc.contributor.authorJaton, B.-
dc.contributor.authorBakkard, D.-
dc.contributor.authorTurunen, H.-
dc.contributor.authorKilkku, O.-
dc.contributor.authorPohjanjousi, P.-
dc.contributor.authorVoima, O.-
dc.contributor.authorNevalaita, L.-
dc.contributor.authorReich, C.-
dc.contributor.authorAraujo, S.-
dc.contributor.authorLongden-Chapman, E.-
dc.contributor.authorBurke, D.-
dc.contributor.authorAgapow, P.-
dc.contributor.authorDerkits, S.-
dc.contributor.authorLicour, M.-
dc.contributor.authorMcCrea, C.-
dc.contributor.authorPayne, S.-
dc.contributor.authorYong, A.-
dc.contributor.authorThompson, L.-
dc.contributor.authorMare, S. Le-
dc.contributor.authorBussmann, M.-
dc.contributor.authorKotik, D.-
dc.date.accessioned2023-07-25T03:22:59Z-
dc.date.available2023-07-25T03:22:59Z-
dc.date.issued2023-
dc.identifier.citationClinical Genitourinary Cancer, 2023, v. 21, n. 2, p. 316.e1-316.e11-
dc.identifier.issn1558-7673-
dc.identifier.urihttp://hdl.handle.net/10722/328887-
dc.description.abstractObjectives: Genome-wide association studies have revealed over 200 genetic susceptibility loci for prostate cancer (PCa). By combining them, polygenic risk scores (PRS) can be generated to predict risk of PCa. We summarize the published evidence and conduct meta-analyses of PRS as a predictor of PCa risk in Caucasian men. Patients and methods: Data were extracted from 59 studies, with 16 studies including 17 separate analyses used in the main meta-analysis with a total of 20,786 cases and 69,106 controls identified through a systematic search of ten databases. Random effects meta-analysis was used to obtain pooled estimates of area under the receiver-operating characteristic curve (AUC). Meta-regression was used to assess the impact of number of single-nucleotide polymorphisms (SNPs) incorporated in PRS on AUC. Heterogeneity is expressed as I2 scores. Publication bias was evaluated using funnel plots and Egger tests. Results: The ability of PRS to identify men with PCa was modest (pooled AUC 0.63, 95% CI 0.62-0.64) with moderate consistency (I2 64%). Combining PRS with clinical variables increased the pooled AUC to 0.74 (0.68-0.81). Meta-regression showed only negligible increase in AUC for adding incremental SNPs. Despite moderate heterogeneity, publication bias was not evident. Conclusion: Typically, PRS accuracy is comparable to PSA or family history with a pooled AUC value 0.63 indicating mediocre performance for PRS alone.-
dc.languageeng-
dc.relation.ispartofClinical Genitourinary Cancer-
dc.subjectGenetic variance-
dc.subjectPolygenic risk score-
dc.subjectProstate cancer risk-
dc.subjectSingle-nucleotide polymorphism-
dc.titleHow Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.clgc.2022.09.006-
dc.identifier.pmid36243664-
dc.identifier.scopuseid_2-s2.0-85151045035-
dc.identifier.volume21-
dc.identifier.issue2-
dc.identifier.spage316.e1-
dc.identifier.epage316.e11-
dc.identifier.eissn1938-0682-
dc.identifier.isiWOS:001167164500001-

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