Rare Germline Variants in ATM Predispose to Prostate Cancer: A PRACTICAL Consortium Study.

Autor: Karlsson Q; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., Brook MN; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., Dadaev T; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., Wakerell S; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., Saunders EJ; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK., Muir K; Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK; Warwick Medical School, University of Warwick, Coventry, UK., Neal DE; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK; Department of Oncology, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK., Giles GG; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia., MacInnis RJ; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia., Thibodeau SN; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., McDonnell SK; Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA., Cannon-Albright L; Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA; George E Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA., Teixeira MR; Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal; Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal; Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal., Paulo P; Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal., Cardoso M; Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal., Huff C; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Li D; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Yao Y; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Scheet P; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Permuth JB; Departments of Cancer Epidemiology and Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA., Stanford JL; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA., Dai JY; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., Ostrander EA; Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA., Cussenot O; GRC n°, AP-HP, Tenon Hospital, Sorbonne Universite, Paris, France; CeRePP, Tenon Hospital, Paris, France., Cancel-Tassin G; GRC n°, AP-HP, Tenon Hospital, Sorbonne Universite, Paris, France; CeRePP, Tenon Hospital, Paris, France., Hoegel J; Institute for Human Genetics, University Hospital Ulm, Ulm, Germany., Herkommer K; Department of Urology, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Schleutker J; Institute of Biomedicine, University of Turku, Turku, Finland; Department of Medical Genetics, Genomics, Laboratory Division, Turku University Hospital, Turku, Finland., Tammela TLJ; Department of Urology, Tampere University Hospital, Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Rathinakannan V; Institute of Biomedicine, University of Turku, Turku, Finland., Sipeky C; Institute of Biomedicine, University of Turku, Turku, Finland., Wiklund F; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden., Grönberg H; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden., Aly M; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital, Solna, Stockholm, Sweden; Department of Urology, Karolinska University Hospital, Solna, Stockholm., Isaacs WB; James Buchanan Brady Urological Institute, Johns Hopkins Hospital and Medical Institution, Baltimore, MD, USA., Dickinson JL; University of Tasmania, Menzies Institute for Medical Research, Hobart, Tasmania, Australia., FitzGerald LM; University of Tasmania, Menzies Institute for Medical Research, Hobart, Tasmania, Australia., Chua MLK; Divisions of Radiation Oncology and Medical Sciences, National Cancer Centre Singapore, Singapore; Duke-NUS Medical School, Singapore., Nguyen-Dumont T; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia; Department of Clinical Pathology, The Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia., Schaid DJ; Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA., Southey MC; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia; Department of Clinical Pathology, The Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia., Eeles RA; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK; Royal Marsden NHS Foundation Trust, London, UK., Kote-Jarai Z; Division of Genetics & Epidemiology, The Institute of Cancer Research, London, UK. Electronic address: zsofia.kote-jarai@icr.ac.uk.
Jazyk: angličtina
Zdroj: European urology oncology [Eur Urol Oncol] 2021 Aug; Vol. 4 (4), pp. 570-579. Date of Electronic Publication: 2021 Jan 09.
DOI: 10.1016/j.euo.2020.12.001
Abstrakt: Background: Germline ATM mutations are suggested to contribute to predisposition to prostate cancer (PrCa). Previous studies have had inadequate power to estimate variant effect sizes.
Objective: To precisely estimate the contribution of germline ATM mutations to PrCa risk.
Design, Setting, and Participants: We analysed next-generation sequencing data from 13 PRACTICAL study groups comprising 5560 cases and 3353 controls of European ancestry.
Outcome Measurements and Statistical Analysis: Variant Call Format files were harmonised, annotated for rare ATM variants, and classified as tier 1 (likely pathogenic) or tier 2 (potentially deleterious). Associations with overall PrCa risk and clinical subtypes were estimated.
Results and Limitations: PrCa risk was higher in carriers of a tier 1 germline ATM variant, with an overall odds ratio (OR) of 4.4 (95% confidence interval [CI]: 2.0-9.5). There was also evidence that PrCa cases with younger age at diagnosis (<65 yr) had elevated tier 1 variant frequencies (p difference  = 0.04). Tier 2 variants were also associated with PrCa risk, with an OR of 1.4 (95% CI: 1.1-1.7).
Conclusions: Carriers of pathogenic ATM variants have an elevated risk of developing PrCa and are at an increased risk for earlier-onset disease presentation. These results provide information for counselling of men and their families.
Patient Summary: In this study, we estimated that men who inherit a likely pathogenic mutation in the ATM gene had an approximately a fourfold risk of developing prostate cancer. In addition, they are likely to develop the disease earlier.
(Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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