Assessment of a Polygenic Risk Score in Screening for Prostate Cancer

作者：Jana McHugh, Elizabeth Bancroft, Edward Saunders, Mark N. Brook, Eva McGrowder, Sarah Wakerell, Denzil James, Reshma Rageevakumar, Barbara Benton, Natalie Taylor, Kathryn Myhill, Matthew Hogben, Netty Kinsella, Aslam Sohaib, Declan Cahill, Stephen Hazell, Samuel J. Withey, Naami Charlotte Mcaddy, Elizabeth Page, Andrea Osborne, Sarah Benafif, Ann-Britt Jones, Dhruv Patel, Dean Y. Huang, Kaljit Kaur, Bradley Russell, Ray Nicholson, Fionnuala Croft, Justyna Sobczak, Claire McNally, F. Mutch, Samantha Bennett, Lenita Kingston, Questa Karlsson, Tokhir Dadaev, Sibel Saya, Susan Merson, Angela Wood, Nening M. Dennis, Nafisa Hussain, Alison Thwaites, Syed Arshad Hussain, Imran Rafi, Michelle Ferris, Pardeep Kumar, Nicholas D. James, Nora Pashayan, Zsofia Kote‐Jarai, Rosalind A. Eeles · 发表于：New England Journal of Medicine · 年份：2025 · DOI：10.1056/nejmoa2407934 · 被引用次数：94 · 研究领域：Prostate Cancer Diagnosis and Treatment、Prostate Cancer Treatment and Research、Genetic Associations and Epidemiology

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, ...