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      Evaluation of a Multiethnic Polygenic Risk Score Model for Prostate Cancer

      brief-report

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          Abstract

          Polygenic risk scores (PRSs) of common genetic variants have shown promise in prostate cancer risk stratification, but their validity across populations has yet to be confirmed. We evaluated a multiethnic PRS model based on 269 germline genetic risk variants (261 were available for analysis) using an independent population of 13 628 US men. The PRS was strongly associated with prostate cancer but not with any other disease. Comparing men in the top PRS decile with those at average risk (40%-60%), the odds ratio of prostate cancer was 3.89 (95% confidence interval = 3.24 to 4.68) for men of European ancestry and 3.81 (95% confidence interval = 1.48 to 10.19) for men of African ancestry. By age 85 years, the cumulative incidence of prostate cancer for European American men was 7.1% in the bottom decile and 54.1% in the top decile. This suggests that the PRS can be used to identify a substantial proportion of men at high risk for prostate cancer.

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          Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study

          Hashim U Ahmed, Ahmed El-Shater Bosaily, Louise C Brown … (2017)
          Men with high serum prostate specific antigen usually undergo transrectal ultrasound-guided prostate biopsy (TRUS-biopsy). TRUS-biopsy can cause side-effects including bleeding, pain, and infection. Multi-parametric magnetic resonance imaging (MP-MRI) used as a triage test might allow men to avoid unnecessary TRUS-biopsy and improve diagnostic accuracy.
          Article 0 comments Cited 740 times – based on 0 reviews     Review now
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            MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis

            Veeru Kasivisvanathan, Antti S. Rannikko, Marcelo Borghi … (2018)
            Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited.
            Article 0 comments Cited 694 times – based on 0 reviews     Review now
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              Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

              Fredrick R. Schumacher, Ali Amin Al Olama, Sonja I. Berndt … (2018)
              Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.
              Article 0 comments Cited 303 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Anna Plym:
                ORCID: https://orcid.org/0000-0001-6351-4744
                Kathryn L Penney:
                ORCID: https://orcid.org/0000-0002-2815-3450
                Sarah Kalia
                Peter Kraft:
                ORCID: https://orcid.org/0000-0002-4472-8103
                David V Conti
                Christopher Haiman
                Lorelei A Mucci:
                ORCID: https://orcid.org/0000-0002-2551-4927
                Adam S Kibel
                Journal
                Journal ID (nlm-ta): J Natl Cancer Inst
                Journal ID (iso-abbrev): J Natl Cancer Inst
                Journal ID (publisher-id): jnci
                Title: JNCI Journal of the National Cancer Institute
                Publisher: Oxford University Press
                ISSN (Print): 0027-8874
                ISSN (Electronic): 1460-2105
                Publication date Collection: May 2022
                Publication date (Electronic): 01 April 2021
                Publication date PMC-release: 01 April 2021
                Volume: 114
                Issue: 5
                Pages: 771-774
                Affiliations
                Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School , Boston, MA, USA
                Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA, USA
                Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm, Sweden
                Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA, USA
                Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, MA, USA
                Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA, USA
                Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA, USA
                Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health , Boston, MA, USA
                Department of Biostatistics, Harvard T.H. Chan School of Public Health , Boston, MA, USA
                Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center , Los Angeles, CA, USA
                Department of Preventive Medicine, Center for Genetic Epidemiology, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center , Los Angeles, CA, USA
                Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA, USA
                Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School , Boston, MA, USA
                Author notes
                Correspondence to: Anna Plym, PhD, Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, 45 Francis St, Boston, MA 02115, USA (e-mail: aplym@ 123456bwh.harvard.edu ).
                Author information
                https://orcid.org/0000-0001-6351-4744
                https://orcid.org/0000-0002-2815-3450
                https://orcid.org/0000-0002-4472-8103
                https://orcid.org/0000-0002-2551-4927
                Article
                Publisher ID: djab058
                DOI: 10.1093/jnci/djab058
                PMC ID: 9086757
                PubMed ID: 33792693
                SO-VID: e68afd42-2c9d-4a29-a04f-150421e16790
                Copyright © © The Author(s) 2021. Published by Oxford University Press.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Date received : 04 January 2021
                Date revision received : 17 February 2021
                Date accepted : 29 March 2021
                Date: 24 May 2021
                Page count
                Pages: 4
                Funding
                Funded by: DiNovi Family Foundation;
                Funded by: National Cancer Institute at the National Institutes of Health;
                Award ID: P30 CA006516
                Award ID: CA 014089
                Funded by: William Casey, the Swedish Society for Medical Research;
                Award ID: P19-0017
                Funded by: Prostate Cancer Foundation, DOI 10.13039/100000892;
                Categories
                Subject: Brief Communications
                Subject: AcademicSubjects/MED00010

                ScienceOpen disciplines: Oncology & Radiotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy

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