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Abstract

Volume 11, Issue 1 (January 2009) 11, 49–55; 10.1038/aja.2008.18

Identification of new genetic risk factors for prostate cancer

Michelle Guy1, Zsofia Kote-Jarai1, Graham G. Giles2,3, Ali Amin Al Olama4, Sarah K. Jugurnauth1, Shani Mulholland1, Daniel A. Leongamornlert1, Stephen M. Edwards1, Jonathan Morrison4, Helen I. Field5, Melissa C. Southey6, Gianluca Severi2,3, Jenny L. Donovan7, Freddie C. Hamdy8, David P. Dearnaley1,9, Kenneth R. Muir10, Charmaine Smith2, Melisa Bagnato2, Audrey T. Ardern-Jones9, Amanda L. Hall1,9, Lynne T. O’Brien1, Beatrice N. Gehr-Swain1,9, Rosemary A. Wilkinson1, Angela Cox11, Sarah Lewis7, Paul M. Brown12, Sameer G. Jhavar1, Malgorzata Tymrakiewicz1, Artitaya Lophatananon10, Sarah L. Bryant1, The UK Genetic Prostate Cancer Study Collaborators13, British Association of Urological Surgeons’Section of Oncology and The UK ProtecT Study Collaborators13, Alan Horwich1,9, Robert A. Huddart1,9, Vincent S. Khoo1,9, Christopher C. Parker1,9, Christopher J. Woodhouse9, Alan Thompson9, Tim Christmas9, Chris Ogden9, Cyril Fisher9, Charles Jameson9, Colin S. Cooper1, Dallas R. English3, John L. Hopper3, David E. Neal12,14, Douglas F. Easton4 and Rosalind A. Eeles1,9

1 Section of Cancer Genetics, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK;
2 Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton VIC 3053, Australia;
3 Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Carlton VIC 3053, Australia;
4 Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK;
5 Department of Oncology, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK;
6 Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville VIC 3052, Australia;
7 Department of Social Medicine, University of Bristol, Bristol BS8 2PR, UK;
8 Academic Urology Unit, University of Sheffield, Sheffield S10 2JF, UK;
9 The Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT and London SW3 6JJ, UK;
10 University of Nottingham Medical School, Queens Medical Centre, Nottingham NG7 2UH, UK;
11 Institute for Cancer Studies, University of Sheffield, Sheffield S10 2RX, UK;
12 Surgical Oncology (Uro-Oncology S4), Departments of Oncology and Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK;
13 A full list of authors is provided in the Supplementary Note online;
14 Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK.

Correspondence: Dr Michelle Guy, Translational Cancer Genetics Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK. Tel: +44-20-8661-3507 E-mail: Michelle.Guy@icr.ac.uk

Received 30 September 2008; Accepted 2 October 2008; Published online 1 December 2008

Abstract

There is evidence that a substantial part of genetic predisposition to prostate cancer (PCa) may be due to lower penetrance genes which are found by genome-wide association studies. We have recently conducted such a study and seven new regions of the genome linked to PCa risk have been identified. Three of these loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for PCa screening, and the LMTK2 gene might provide a potential therapeutic target. Together with results from other groups, there are now 23 germline genetic variants which have been reported. These results have the potential to be developed into a genetic test. However, we consider that marketing of tests to the public is premature, as PCa risk can not be evaluated fully at this stage and the appropriate screening protocols need to be developed. Follow-up validation studies, as well as studies to explore the psychological implications of genetic profile testing, will be vital prior to roll out into healthcare.

Keywords: prostate cancer, genetics, susceptibility loci, SNPs, relative risks

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Asian Journal of Andrology CN 31-1795/R ISSN 1008-682X  Copyright © 2023  Shanghai Materia Medica, Chinese Academy of Sciences.  All rights reserved.