Accès ouvert déclaré 2024 article

A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer

Srilakshmi Srinivasan, Thomas Kryza, Nathalie Bock, Brian Wan-Chi Tse, Kamil A. Sokolowski, Janaththani Panchadsaram, Achala Fernando, Leire Moya, Carson Stephens, Ying Dong, Joan Röhl, Saeid Alinezhad, Ian Vela, Joanna Perry‐Keene, Katie Buzacott, Robert Nica, Elizabeth Bancroft, Elizabeth Page, Audrey Ardern‐Jones, Chris Bangma, Elena Castro, David P. Dearnaley, Diana Eccles, D. Gareth Evans, Jórunn E. Eyfjörd, Alison Falconer, Christopher S. Foster, Freddie C. Hamdy, Óskar Þór Jóhannsson, Vincent Khoo, Geoffrey J. Lindeman, Jan Lubiński, Lovise Mæhle, Christos Mikropoulos, Anita Mitra, Clare Moynihan, Judith Offman, Gad Rennert, Lucy Side, Mohnish Suri, Penny Wilson, Manuela Gago-Domínguez, Pardeep Kumar, Antonis C. Antoniou, Jana McHugh, Holly Ní Raghallaigh, R. R. Hall, Natalie Taylor, Sarah Thomas, Kathryn Myhill, Matthew Hogben, Eva McGrowder, Diana Keating, Denzil James, Syed Arshad Hussain, Angela Wood, Nening M. Dennis, Paul Ardern-Jones, N. van As, Steve Hazell, Sarah J. Lewis, Paul D.P. Pharoah, J. Schalken, Aslam Sohaib, Nandita de Souza, Paul Cathcart, Frank Chingewundoh, Jeff Bamber, Alexander Dias, Christos Mikropolis, Sibel Saya, Anne-Marie Borges Da Silva, Lucia D’Mello, Sue Moss, J Melia, Netty Kinsella, Justyna Sobczak, Naami Mcaddy, David Nicol, Chris Ogden, Declan Cahill, Alan Thompson, Christopher Woodhouse, Vincent J. Gnanapragasam, Colin Cooper, Jeremy Clark, Johanna Schleutker, Christiane Maier, Kenneth Muir, Catherine M. Tangen, Henrik Grönberg, Nora Pashayan, Demetrius Albanes, Alicja Wolk, Janet L. Stanford, S.I. Berndt, Lorelei A. Mucci, Stella Koutros, Olivier Cussenot, Karina D. Sørensen, Eli Marie Grindedal, Ruth C. Travis, Christopher A. Haiman, Robert J. MacInnis, Ana Vega, Fredrik Wiklund, David E. Neal, Manolis Kogevinas, Kathryn L. Penney, Børge G. Nordestgaard, Hermann Brenner, Esther M. John, Marija Gamulin, Frank Claessens, Olle Melander, Anders Dahlin, Pär Stattin, Göran Hallmans, Christel Häggström, Robert Johansson, Elin Thysell, Ann‐Charlotte Rönn, Weiqiang Li, Nigel N. Brown, Goce Dimeski, Benjamin Shepherd, Tokhir Dadaev, Mark N. Brook, Amanda B. Spurdle, Ulf‐Håkan Stenman, Hannu Koistinen, Zsofia Kote‐Jarai, Robert J. Klein, Hans Lilja, Rupert Ecker, Rosalind A. Eeles, Fredrick R. Schumacher, Sara Benlloch, Ali Amin Al Olama, Stephen Chanock, Ying Wang, Stephanie J. Weinstein, Catharine West, Géraldine Cancel‐Tassin, Jenny L. Donovan, Robert J. Hamilton, Sue A. Ingles, Barry S. Rosenstein, Yong‐Jie Lu, Graham G. Giles, Adam S. Kibel, Jong Y. Park, Cezary Cybulski, Sune F. Nielsen, Jeri Kim, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Razack, Lisa F. Newcomb, Davor Lessel, Radka Kaneva, Nawaid Usmani, Paul A. Townsend, Jose E. Castelao, F. Ménégaux, Kay-Tee Khaw, Lisa Cannon‐Albright, Hardev Pandha, S. N. Thibodeau, Peter Kraft, William J. Blot, Artitaya Lophatananon, Phyllis J. Goodman, Ian M. Thompson, Tobias Nordström, Alison M. Dunning, Teuvo L.J. Tammela, Anssi Auvinen, Niclas Håkansson, Gerald L. Andriole, Robert N. Hoover, Mitchell J. Machiela, Edward L. Giovannucci, Laura E. Beane Freeman, Michael Borre, Timothy J. Key, Loı̈c Le Marchand, Xin Sheng, Melissa C. Southey, Roger L. Milne, Antonio Gómez‐Caamaño, Laura Fachal, Martin Eklund, Trinidad Dierssen‐Sotos, Gemma Castaño‐Vinyals, Antonio Alcaraz, Sara Lindström, Meir J. Stampfer, Stig E. Bojesen, Hein Vincent Stroomberg, Martin Andreas Røder, Xin Gao, Bernd Holleczek, Ben Schöttker, Josef Hoegel, Thomas Schnoeller, Tomislav Kuliš, Steven Joniau, Maria Elena Martinez, Markus Aly, Wayne D. Tilley, Gail P. Risbridger, Lisa G. Horvath, Renea A. Taylor, Lisa M. Butler, Anne-Maree Haynes, Melissa Papargiris, Judith A. Clements, Jyotsna Batra

15Citations signalées, ce qui n’est pas une note de qualité

155Institutions déclarées

19Pays d’affiliation déclarés

Rattachement africain : au, gb, nl, es, is, pl, no, us, fi, de, se, fr, dk, hr, be, ca, pt, my, bg. Niveau de preuve : code pays fourni par la source.

Le résumé fourni par la source

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T > C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity mediates prostate cancer pathogenesis. The 'Thr' PSA variant leads to small subcutaneous tumours, supporting reduced prostate cancer risk. However, 'Thr' PSA also displays higher metastatic potential with pronounced osteolytic activity in an experimental metastasis in-vivo model. Biochemical characterisation of this PSA variant demonstrates markedly reduced proteolytic activity that correlates with differences in in-vivo tumour burden. The SNP is associated with increased risk for aggressive disease and prostate cancer-specific mortality in three independent cohorts, highlighting its critical function in mediating metastasis. Carriers of this SNP allele have reduced serum total PSA and a higher free/total PSA ratio that could contribute to late biopsy decisions and delay in diagnosis. Our results provide a molecular explanation for the prominent 19q13.3 KLK locus, rs17632542 SNP, association with a spectrum of prostate cancer clinical outcomes.

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Le contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref: A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer
Date Crossref: 06/11/2024
Éditeur: Springer Science and Business Media LLC
Type: journal-article

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.

Les institutions déclarées

Translational Research Institute Queensland University of Technology The University of Queensland Mater Research Florey Institute of Neuroscience and Mental Health Bond University Princess Alexandra Hospital Sunshine Coast University Hospital Royal Marsden NHS Foundation Trust Institute of Cancer Research Erasmus MC Spanish National Cancer Research Centre Centro de Investigación del Cáncer University of Southampton St Mary's Hospital University of Iceland Imperial College Healthcare NHS Trust University of Liverpool University of Oxford John Radcliffe Hospital National University Hospital of Iceland Walter and Eliza Hall Institute of Medical Research International Hereditary Cancer Center Oslo University Hospital Medway Maritime Hospital University College London Hospitals NHS Foundation Trust University College London Queen Mary University of London Guy's Hospital Wessex Regional Genetics Laboratory Nottingham City Hospital Innovate UK Fundación Pública Galega de Medicina Xenómica Servicio Gallego de Salud University of Cambridge University of Bristol Cedars-Sinai Medical Center Radboud University Nijmegen Barts Health NHS Trust St George’s University Hospitals NHS Foundation Trust Cambridge University Hospitals NHS Foundation Trust University of East Anglia University of Turku Turku University Hospital Praxis für Humangenetik Tübingen Manchester Academic Health Science Centre University of Manchester Fred Hutch Cancer Center Karolinska Institutet National Cancer Institute Division of Cancer Epidemiology and Genetics University of Washington Harvard University Sorbonne Université Assistance Publique – Hôpitaux de Paris Hôpital Tenon Onco-Urologie Prédictive Aarhus University Hospital University of Southern California The University of Melbourne Cancer Council Victoria Centre for Biomedical Network Research on Rare Diseases Instituto de Investigación Sanitaria de Santiago Instituto de Investigación de Enfermedades Raras Cancer Research UK Addenbrooke's Hospital Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública Brigham and Women's Hospital Universitat Pompeu Fabra Hospital Del Mar Municipal Institute for Medical Research Barcelona Institute for Global Health University of Copenhagen Gentofte Hospital German Cancer Research Center Heidelberg University Stanford University University of Zagreb KU Leuven Lund University Umeå University Karolinska University Hospital Icahn School of Medicine at Mount Sinai QIMR Berghofer Medical Research Institute University of Helsinki Helsinki University Hospital Memorial Sloan Kettering Cancer Center University Hospitals Seidman Cancer Center Case Western Reserve University American Cancer Society The Christie Hospital The Christie NHS Foundation Trust University of Toronto Princess Margaret Cancer Centre Monash Health Monash University Moffitt Cancer Center Pomeranian Medical University The University of Texas MD Anderson Cancer Center Universidade do Porto Instituto Português de Oncologia Francisco Gentil IPO Porto City of Hope Beckman Research Institute Ghent University University of Malaya Universität Hamburg University Medical Center Hamburg-Eppendorf Medical University of Sofia University of Alberta Health Innovation Manchester NIHR Manchester Biomedical Research Centre University Hospital Complex Of Vigo University of Surrey Complexo Hospitalario Universitario A Coruña Inserm Université Paris-Saclay Institut Gustave Roussy Centre de recherche en Epidémiologie et Santé des Populations University of Utah George E. Wahlen Department of VA Medical Center Mayo Clinic in Arizona International Epidemiology Institute Vanderbilt University Medical Center Christus Santa Rosa Health System Tampere University Tampere University Hospital Tampere University Washington University in St. Louis Aarhus University University of Hawaiʻi at Mānoa University of Hawaii System Cancer Center of Hawaii University of Hawaii Cancer Center Melbourne Clinic Complejo Hospitalario Universitario de Santiago Universidad de Cantabria Instituto de Investigación Marqués de Valdecilla Consorci Institut D'Investigacions Biomediques August Pi I Sunyer Universitat de Barcelona Copenhagen University Hospital Rigshospitalet Krebsregister Saarland University Hospital Ulm University Hospital Centre Zagreb University of California San Diego Centre for Cancer Biology The University of Adelaide Peter MacCallum Cancer Centre Chris O’Brien Lifehouse Garvan Institute of Medical Research South Australian Health and Medical Research Institute Freemasons Foundation Centre for Men's Health Discovery Institute The Kinghorn Cancer Centre

Une affiliation ne permet pas de déduire la nationalité d’un auteur.

Les sujets associés

Prostate Cancer Treatment and ResearchProstate Cancer Diagnosis and TreatmentCancer-related molecular mechanisms research

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