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Identific.tion of new genetic.risk fac.ors for prostate c.nc.r

Asian Journal of Andrology 2009年第1期11卷 49-55页

作者： Mic.elle Guy Zsofia Kote-Jarai Graham G. Giles Ali Amin Al Olama Sarah K. Jugurnauth Shani Mulholland Daniel A. Leongamomlert Stephen M. Edwards Jonathan Morrison Helen I. Field melissa c. southey Gianluc. Severi Jenny L. Donovan Freddie c. Hamdy David R Dearnaley Kenneth R. Muir c.armaine Smith Melisa Bagnato Audrey T. Ardern-Jones Amanda L. Hall Lynne T. O＇Brien Beatric. N. Gehr-Swain Rosemary A. Wilkinson Angela c.x Sarah Lewis Paul M. Brown Sameer G. Jhavar Malgorzata Tymrakiewic. Artitaya Lophatananon Sarah L. Bryant The UK Genetic.Prostate c.nc.r Study c.llaborators British Assoc.ation of Urologic.l Surgeons＇ Sec.ion of Onc.logy and The UK Protec. Study c.llaborators Alan Horwic. Robert A. Huddart Vinc.nt S. Khoo c.ristopher c. Parker c.ristopher J. Woodhouse Alan Thompson Tim c.ristmas c.ris Ogden c.ril Fisher c.arles Jameson c.lin S. c.oper Dallas R. English John L. Hopper David E. Neal Douglas E Easton Rosalind A. Eeles Sec.ion of c.nc.r Genetic. The Institute of Cancer Research Sutton Surrey SM2 5NG UK c.nc.r Epidemiology c.ntre The Cancer Council Victoria Carlton VIC 3053 Australia c.ntre for Molec.lar Environmental Genetic and Analytic Epidemiology The University of Melbourne Carlton VIC 3053 Australia c.nc.r Researc. UK Genetic.Epidemiology Unit University of Cambridge Strangeways Laboratory Worts Causeway Cambridge CB1 8RN UK Department of Onc.logy University of Cambridge Strangeways Laboratory Worts Causeway Cambridge CB1 8RN UK Genetic.Epidemiology Laboratory Department of Pathology The University of Melbourne Parkville VIC 3052 Australia Department of Soc.al Medic.ne University of Bristol Bristol BS8 2PR UK Ac.demic.Urology Unit University of Sheffield Sheffield SIO 2JF UK The Royal Marsden NHS Foundation Trust Sutton Surrey SM2 5PT and London SW3 6JJ UK University of Nottingham Medic.l Sc.ool Queens Medical Centre Nottingham NG7 2UH UK Institute for c.nc.r Studies University of Sheffield Sheffield SIO 2RX UK Surgic.l Onc.logy （Uro-Onc.logy S4） Departments of Oncology and Surgery University of Cambridge Addenbrooke＇s Hospital Cambridge CB2 2QQ UK A full list of authors is provided in the Supplementary Note online Ka Shing Centre Cambridge CB2 ORE UK c.nc.r Researc. UK c.mbridge Researc. Institute Li Ka Shing Centre Cambridge CB2 ORE UK.

There is evidenc. that a substantial part of genetic.predisposition to prostate c.nc.r （Pc.） may be due to lower penetranc. genes whic. are found by genome-wide assoc.ation studies. We have rec.ntly c.nduc.ed suc. a study and seven new regions of the genome linked to Pc. risk have been identified. Three of these loc. c.ntain c.ndidate susc.ptibility genes： MSMB, LMTK2 and KLK2/3. The MSMB and KLK2/3 genes may be useful for Pc. sc.eening, and the LMTK2 gene might provide a potential therapeutic.target. Together with results from other groups, there are now 23 germline genetic.variants whic. have been reported. These results have the potential to be developed into a genetic.test. However, we c.nsider that marketing of tests to the public.is premature, as Pc. risk c.n not be evaluated fully at this stage and the appropriate sc.eening protoc.ls need to be developed. Follow-up validation studies, as well as studies to explore the psyc.ologic.l implic.tions of genetic.profile testing, will be vital prior to roll out into healthc.re.

关键词： prostate c.nc.r genetic. susc.ptibility loc. SNPs relative risks

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