| Title: |
Assessment of a Polygenic Risk Score in Screening for Prostate Cancer. |
| Authors: |
McHugh, JK; Bancroft, EK; Saunders, E; Brook, MN; McGrowder, E; Wakerell, S; James, D; Rageevakumar, R; Benton, B; Taylor, N; Myhill, K; Hogben, M; Kinsella, N; Sohaib, AA; Cahill, D; Hazell, S; Withey, SJ; Mcaddy, N; Page, EC; Osborne, A; Benafif, S; Jones, A-B; Patel, D; Huang, DY; Kaur, K; Russell, B; Nicholson, R; Croft, F; Sobczak, J; McNally, C; Mutch, F; Bennett, S; Kingston, L; Karlsson, Q; Dadaev, T; Saya, S; Merson, S; Wood, A; Dennis, N; Hussain, N; Thwaites, A; Hussain, S; Rafi, I; Ferris, M; Kumar, P; James, ND; Pashayan, N; Kote-Jarai, Z; Eeles, RA; BARCODE1 Steering Committee and Collaborators |
| Contributors: |
Saunders, Edward; Brook, Mark; James, Nicholas; Kote-Jarai, Zsofia; Eeles, Rosalind |
| Publisher Information: |
MASSACHUSETTS MEDICAL SOC |
| Publication Year: |
2025 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
Aged; Humans; Male; Middle Aged; Biopsy; Early Detection of Cancer; Genetic Predisposition to Disease; Genetic Risk Score; Genome-Wide Association Study; Multifactorial Inheritance; Multiparametric Magnetic Resonance Imaging; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Assessment; Saliva; United Kingdom; Case-Control Studies; Prospective Studies |
| Subject Geographic: |
United States |
| Description: |
BACKGROUND: The incidence of prostate cancer is increasing. Screening with an assay of prostate-specific antigen (PSA) has a high rate for false positive results. Genomewide association studies have identified common germline variants in persons with prostate cancer, which can be used to calculate a polygenic risk score associated with risk of prostate cancer. METHODS: We recruited persons 55 to 69 years of age from primary care centers in the United Kingdom. Using germline DNA extracted from saliva, we derived polygenic risk scores from 130 variants known to be associated with an increased risk of prostate cancer. Participants with a polygenic risk score in the 90th percentile or higher were invited to undergo prostate cancer screening with multiparametric magnetic resonance imaging (MRI) and transperineal biopsy, irrespective of PSA level. RESULTS: Among 40,292 persons invited to participate, 8953 (22.2%) expressed interest in participating and 6393 had their polygenic risk score calculated; 745 (11.7%) had a polygenic risk score in the 90th percentile or higher and were invited to undergo screening. Of these 745 participants, 468 (62.8%) underwent MRI and prostate biopsy; prostate cancer was detected in 187 participants (40.0%). The median age at diagnosis was 64 years (range, 57 to 73). Of the 187 participants with cancer, 103 (55.1%) had prostate cancer classified as intermediate or higher risk according to the 2024 National Comprehensive Cancer Network (NCCN) criteria, so treatment was indicated; cancer would not have been detected in 74 (71.8%) of these participants according to the prostate cancer diagnostic pathway currently used in the United Kingdom (high PSA level and positive MRI results). In addition, 40 of the participants with cancer (21.4%) had disease classified as unfavorable intermediate risk or as high or very high risk according to NCCN criteria. CONCLUSIONS: In a prostate cancer screening program involving participants in the top decile of risk as determined by a polygenic risk score, the ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print; 1417; application/pdf |
| Language: |
English |
| ISSN: |
1533-4406; 0028-4793 |
| Relation: |
New England Journal of Medicine, 2025, 392 (14), pp. 1406 - 1417; https://repository.icr.ac.uk/handle/internal/6671 |
| DOI: |
10.1056/NEJMoa2407934 |
| Availability: |
https://doi.org/10.1056/NEJMoa2407934; https://repository.icr.ac.uk/handle/internal/6671 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.51B8A2BD |
| Database: |
BASE |