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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Common breast cancer susceptibility alleles and the risk of breast cancer for <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers: implications for risk prediction</title><author><name sortKey="Antoniou, Antonis C" sort="Antoniou, Antonis C" uniqKey="Antoniou A" first="Antonis C" last="Antoniou">Antonis C. Antoniou</name><affiliation><nlm:aff id="A1">Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Beesley, Jonathan" sort="Beesley, Jonathan" uniqKey="Beesley J" first="Jonathan" last="Beesley">Jonathan Beesley</name><affiliation><nlm:aff id="A2">Queensland Institute of Medical Research; Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Mcguffog, Lesley" sort="Mcguffog, Lesley" uniqKey="Mcguffog L" first="Lesley" last="Mcguffog">Lesley Mcguffog</name><affiliation><nlm:aff id="A1">Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Sinilnikova, Olga M" sort="Sinilnikova, Olga M" uniqKey="Sinilnikova O" first="Olga M." last="Sinilnikova">Olga M. Sinilnikova</name><affiliation><nlm:aff id="A3">Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Hospitalier Universitaire de Lyon / Centre Léon Bérard, Lyon, France;</nlm:aff></affiliation></author><author><name sortKey="Healey, Sue" sort="Healey, Sue" uniqKey="Healey S" first="Sue" last="Healey">Sue Healey</name><affiliation><nlm:aff id="A2">Queensland Institute of Medical Research; Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Neuhausen, Susan L" sort="Neuhausen, Susan L" uniqKey="Neuhausen S" first="Susan L." last="Neuhausen">Susan L. Neuhausen</name><affiliation><nlm:aff id="A4">Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA USA</nlm:aff></affiliation></author><author><name sortKey="Ding, Yuan Chun" sort="Ding, Yuan Chun" uniqKey="Ding Y" first="Yuan Chun" last="Ding">Yuan Chun Ding</name><affiliation><nlm:aff id="A4">Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA USA</nlm:aff></affiliation></author><author><name sortKey="Rebbeck, Timothy R" sort="Rebbeck, Timothy R" uniqKey="Rebbeck T" first="Timothy R." last="Rebbeck">Timothy R. Rebbeck</name><affiliation><nlm:aff id="A5">Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania School of Medicine, Philadelphia, PA</nlm:aff></affiliation></author><author><name sortKey="Weitzel, Jeffrey N" sort="Weitzel, Jeffrey N" uniqKey="Weitzel J" first="Jeffrey N." last="Weitzel">Jeffrey N. Weitzel</name><affiliation><nlm:aff id="A6">City of Hope National Medical Center, Duarte, CA</nlm:aff></affiliation></author><author><name sortKey="Lynch, Henry T" sort="Lynch, Henry T" uniqKey="Lynch H" first="Henry T." last="Lynch">Henry T. Lynch</name><affiliation><nlm:aff id="A7">Creighton University, Omaha, NE</nlm:aff></affiliation></author><author><name sortKey="Isaacs, Claudine" sort="Isaacs, Claudine" uniqKey="Isaacs C" first="Claudine" last="Isaacs">Claudine Isaacs</name><affiliation><nlm:aff id="A8">Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC</nlm:aff></affiliation></author><author><name sortKey="Ganz, Patricia A" sort="Ganz, Patricia A" uniqKey="Ganz P" first="Patricia A." last="Ganz">Patricia A. Ganz</name><affiliation><nlm:aff id="A9">Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, CA</nlm:aff></affiliation></author><author><name sortKey="Tomlinson, Gail" sort="Tomlinson, Gail" uniqKey="Tomlinson G" first="Gail" last="Tomlinson">Gail Tomlinson</name><affiliation><nlm:aff id="A10">University of Texas Health Science Center, San Antonio, TX</nlm:aff></affiliation></author><author><name sortKey="Olopade, Olufunmilayo I" sort="Olopade, Olufunmilayo I" uniqKey="Olopade O" first="Olufunmilayo I." last="Olopade">Olufunmilayo I. Olopade</name><affiliation><nlm:aff id="A11">University of Chicago Medical Center, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J." last="Couch">Fergus J. Couch</name><affiliation><nlm:aff id="A12">Department of Laboratory Medicine and Pathology, Mayo Clinic, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Wang, Xianshu" sort="Wang, Xianshu" uniqKey="Wang X" first="Xianshu" last="Wang">Xianshu Wang</name><affiliation><nlm:aff id="A12">Department of Laboratory Medicine and Pathology, Mayo Clinic, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Lindor, Noralane M" sort="Lindor, Noralane M" uniqKey="Lindor N" first="Noralane M." last="Lindor">Noralane M. Lindor</name><affiliation><nlm:aff id="A13">Department of Medical Genetics, Mayo Clinic, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Pankratz, Vernon S" sort="Pankratz, Vernon S" uniqKey="Pankratz V" first="Vernon S." last="Pankratz">Vernon S. Pankratz</name><affiliation><nlm:aff id="A14">Department of Health Sciences Research, Mayo Clinic, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Radice, Paolo" sort="Radice, Paolo" uniqKey="Radice P" first="Paolo" last="Radice">Paolo Radice</name><affiliation><nlm:aff id="A15">Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Manoukian, Siranoush" sort="Manoukian, Siranoush" uniqKey="Manoukian S" first="Siranoush" last="Manoukian">Siranoush Manoukian</name><affiliation><nlm:aff id="A16">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Peissel, Bernard" sort="Peissel, Bernard" uniqKey="Peissel B" first="Bernard" last="Peissel">Bernard Peissel</name><affiliation><nlm:aff id="A16">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Zaffaroni, Daniela" sort="Zaffaroni, Daniela" uniqKey="Zaffaroni D" first="Daniela" last="Zaffaroni">Daniela Zaffaroni</name><affiliation><nlm:aff id="A16">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Barile, Monica" sort="Barile, Monica" uniqKey="Barile M" first="Monica" last="Barile">Monica Barile</name><affiliation><nlm:aff id="A17">Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Viel, Alessandra" sort="Viel, Alessandra" uniqKey="Viel A" first="Alessandra" last="Viel">Alessandra Viel</name><affiliation><nlm:aff id="A18">Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano (PN), Italy.</nlm:aff></affiliation></author><author><name sortKey="Allavena, Anna" sort="Allavena, Anna" uniqKey="Allavena A" first="Anna" last="Allavena">Anna Allavena</name><affiliation><nlm:aff id="A19">Department of Genetics, Biology and Biochemestry, University of Turin, Turin, Italy</nlm:aff></affiliation></author><author><name sortKey="Dall Lio, Valentina" sort="Dall Lio, Valentina" uniqKey="Dall Lio V" first="Valentina" last="Dall Lio">Valentina Dall Lio</name><affiliation><nlm:aff id="A20">Cogentech, Consortium for Genomics Technology, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Peterlongo, Paolo" sort="Peterlongo, Paolo" uniqKey="Peterlongo P" first="Paolo" last="Peterlongo">Paolo Peterlongo</name><affiliation><nlm:aff id="A15">Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Szabo, Csilla I" sort="Szabo, Csilla I" uniqKey="Szabo C" first="Csilla I." last="Szabo">Csilla I. Szabo</name><affiliation><nlm:aff id="A21">Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Zikan, Michal" sort="Zikan, Michal" uniqKey="Zikan M" first="Michal" last="Zikan">Michal Zikan</name><affiliation><nlm:aff id="A22">Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic</nlm:aff></affiliation></author><author><name sortKey="Claes, Kathleen" sort="Claes, Kathleen" uniqKey="Claes K" first="Kathleen" last="Claes">Kathleen Claes</name><affiliation><nlm:aff id="A23">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Poppe, Bruce" sort="Poppe, Bruce" uniqKey="Poppe B" first="Bruce" last="Poppe">Bruce Poppe</name><affiliation><nlm:aff id="A23">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Foretova, Lenka" sort="Foretova, Lenka" uniqKey="Foretova L" first="Lenka" last="Foretova">Lenka Foretova</name><affiliation><nlm:aff id="A24">Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic</nlm:aff></affiliation></author><author><name sortKey="Mai, Phuong L" sort="Mai, Phuong L" uniqKey="Mai P" first="Phuong L." last="Mai">Phuong L. Mai</name><affiliation><nlm:aff id="A25">Clinical Genetics Branch, US National Cancer Institute, Rockville, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Greene, Mark H" sort="Greene, Mark H" uniqKey="Greene M" first="Mark H." last="Greene">Mark H. Greene</name><affiliation><nlm:aff id="A25">Clinical Genetics Branch, US National Cancer Institute, Rockville, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Rennert, Gad" sort="Rennert, Gad" uniqKey="Rennert G" first="Gad" last="Rennert">Gad Rennert</name><affiliation><nlm:aff id="A26">Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel</nlm:aff></affiliation></author><author><name sortKey="Lejbkowicz, Flavio" sort="Lejbkowicz, Flavio" uniqKey="Lejbkowicz F" first="Flavio" last="Lejbkowicz">Flavio Lejbkowicz</name><affiliation><nlm:aff id="A26">Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel</nlm:aff></affiliation></author><author><name sortKey="Glendon, Gord" sort="Glendon, Gord" uniqKey="Glendon G" first="Gord" last="Glendon">Gord Glendon</name><affiliation><nlm:aff id="A27">Ontario Cancer Genetics Network (OCGN), Cancer Care Ontario</nlm:aff></affiliation></author><author><name sortKey="Ozcelik, Hilmi" sort="Ozcelik, Hilmi" uniqKey="Ozcelik H" first="Hilmi" last="Ozcelik">Hilmi Ozcelik</name><affiliation><nlm:aff id="A28">Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L." last="Andrulis">Irene L. Andrulis</name><affiliation><nlm:aff id="A27">Ontario Cancer Genetics Network (OCGN), Cancer Care Ontario</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21118973</idno><idno type="pmc">2999830</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999830</idno><idno type="RBID">PMC:2999830</idno><idno type="doi">10.1158/0008-5472.CAN-10-1907</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">001F11</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001F11</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Common breast cancer susceptibility alleles and the risk of breast cancer for <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers: implications for risk prediction</title><author><name sortKey="Antoniou, Antonis C" sort="Antoniou, Antonis C" uniqKey="Antoniou A" first="Antonis C" last="Antoniou">Antonis C. Antoniou</name><affiliation><nlm:aff id="A1">Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Beesley, Jonathan" sort="Beesley, Jonathan" uniqKey="Beesley J" first="Jonathan" last="Beesley">Jonathan Beesley</name><affiliation><nlm:aff id="A2">Queensland Institute of Medical Research; Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Mcguffog, Lesley" sort="Mcguffog, Lesley" uniqKey="Mcguffog L" first="Lesley" last="Mcguffog">Lesley Mcguffog</name><affiliation><nlm:aff id="A1">Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, UK</nlm:aff></affiliation></author><author><name sortKey="Sinilnikova, Olga M" sort="Sinilnikova, Olga M" uniqKey="Sinilnikova O" first="Olga M." last="Sinilnikova">Olga M. Sinilnikova</name><affiliation><nlm:aff id="A3">Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Hospitalier Universitaire de Lyon / Centre Léon Bérard, Lyon, France;</nlm:aff></affiliation></author><author><name sortKey="Healey, Sue" sort="Healey, Sue" uniqKey="Healey S" first="Sue" last="Healey">Sue Healey</name><affiliation><nlm:aff id="A2">Queensland Institute of Medical Research; Brisbane, Australia</nlm:aff></affiliation></author><author><name sortKey="Neuhausen, Susan L" sort="Neuhausen, Susan L" uniqKey="Neuhausen S" first="Susan L." last="Neuhausen">Susan L. Neuhausen</name><affiliation><nlm:aff id="A4">Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA USA</nlm:aff></affiliation></author><author><name sortKey="Ding, Yuan Chun" sort="Ding, Yuan Chun" uniqKey="Ding Y" first="Yuan Chun" last="Ding">Yuan Chun Ding</name><affiliation><nlm:aff id="A4">Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA USA</nlm:aff></affiliation></author><author><name sortKey="Rebbeck, Timothy R" sort="Rebbeck, Timothy R" uniqKey="Rebbeck T" first="Timothy R." last="Rebbeck">Timothy R. Rebbeck</name><affiliation><nlm:aff id="A5">Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania School of Medicine, Philadelphia, PA</nlm:aff></affiliation></author><author><name sortKey="Weitzel, Jeffrey N" sort="Weitzel, Jeffrey N" uniqKey="Weitzel J" first="Jeffrey N." last="Weitzel">Jeffrey N. Weitzel</name><affiliation><nlm:aff id="A6">City of Hope National Medical Center, Duarte, CA</nlm:aff></affiliation></author><author><name sortKey="Lynch, Henry T" sort="Lynch, Henry T" uniqKey="Lynch H" first="Henry T." last="Lynch">Henry T. Lynch</name><affiliation><nlm:aff id="A7">Creighton University, Omaha, NE</nlm:aff></affiliation></author><author><name sortKey="Isaacs, Claudine" sort="Isaacs, Claudine" uniqKey="Isaacs C" first="Claudine" last="Isaacs">Claudine Isaacs</name><affiliation><nlm:aff id="A8">Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC</nlm:aff></affiliation></author><author><name sortKey="Ganz, Patricia A" sort="Ganz, Patricia A" uniqKey="Ganz P" first="Patricia A." last="Ganz">Patricia A. Ganz</name><affiliation><nlm:aff id="A9">Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, CA</nlm:aff></affiliation></author><author><name sortKey="Tomlinson, Gail" sort="Tomlinson, Gail" uniqKey="Tomlinson G" first="Gail" last="Tomlinson">Gail Tomlinson</name><affiliation><nlm:aff id="A10">University of Texas Health Science Center, San Antonio, TX</nlm:aff></affiliation></author><author><name sortKey="Olopade, Olufunmilayo I" sort="Olopade, Olufunmilayo I" uniqKey="Olopade O" first="Olufunmilayo I." last="Olopade">Olufunmilayo I. Olopade</name><affiliation><nlm:aff id="A11">University of Chicago Medical Center, Chicago, IL</nlm:aff></affiliation></author><author><name sortKey="Couch, Fergus J" sort="Couch, Fergus J" uniqKey="Couch F" first="Fergus J." last="Couch">Fergus J. Couch</name><affiliation><nlm:aff id="A12">Department of Laboratory Medicine and Pathology, Mayo Clinic, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Wang, Xianshu" sort="Wang, Xianshu" uniqKey="Wang X" first="Xianshu" last="Wang">Xianshu Wang</name><affiliation><nlm:aff id="A12">Department of Laboratory Medicine and Pathology, Mayo Clinic, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Lindor, Noralane M" sort="Lindor, Noralane M" uniqKey="Lindor N" first="Noralane M." last="Lindor">Noralane M. Lindor</name><affiliation><nlm:aff id="A13">Department of Medical Genetics, Mayo Clinic, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Pankratz, Vernon S" sort="Pankratz, Vernon S" uniqKey="Pankratz V" first="Vernon S." last="Pankratz">Vernon S. Pankratz</name><affiliation><nlm:aff id="A14">Department of Health Sciences Research, Mayo Clinic, Minnesota, USA</nlm:aff></affiliation></author><author><name sortKey="Radice, Paolo" sort="Radice, Paolo" uniqKey="Radice P" first="Paolo" last="Radice">Paolo Radice</name><affiliation><nlm:aff id="A15">Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Manoukian, Siranoush" sort="Manoukian, Siranoush" uniqKey="Manoukian S" first="Siranoush" last="Manoukian">Siranoush Manoukian</name><affiliation><nlm:aff id="A16">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Peissel, Bernard" sort="Peissel, Bernard" uniqKey="Peissel B" first="Bernard" last="Peissel">Bernard Peissel</name><affiliation><nlm:aff id="A16">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Zaffaroni, Daniela" sort="Zaffaroni, Daniela" uniqKey="Zaffaroni D" first="Daniela" last="Zaffaroni">Daniela Zaffaroni</name><affiliation><nlm:aff id="A16">Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Barile, Monica" sort="Barile, Monica" uniqKey="Barile M" first="Monica" last="Barile">Monica Barile</name><affiliation><nlm:aff id="A17">Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Viel, Alessandra" sort="Viel, Alessandra" uniqKey="Viel A" first="Alessandra" last="Viel">Alessandra Viel</name><affiliation><nlm:aff id="A18">Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano (PN), Italy.</nlm:aff></affiliation></author><author><name sortKey="Allavena, Anna" sort="Allavena, Anna" uniqKey="Allavena A" first="Anna" last="Allavena">Anna Allavena</name><affiliation><nlm:aff id="A19">Department of Genetics, Biology and Biochemestry, University of Turin, Turin, Italy</nlm:aff></affiliation></author><author><name sortKey="Dall Lio, Valentina" sort="Dall Lio, Valentina" uniqKey="Dall Lio V" first="Valentina" last="Dall Lio">Valentina Dall Lio</name><affiliation><nlm:aff id="A20">Cogentech, Consortium for Genomics Technology, Milan, Italy</nlm:aff></affiliation></author><author><name sortKey="Peterlongo, Paolo" sort="Peterlongo, Paolo" uniqKey="Peterlongo P" first="Paolo" last="Peterlongo">Paolo Peterlongo</name><affiliation><nlm:aff id="A15">Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.</nlm:aff></affiliation></author><author><name sortKey="Szabo, Csilla I" sort="Szabo, Csilla I" uniqKey="Szabo C" first="Csilla I." last="Szabo">Csilla I. Szabo</name><affiliation><nlm:aff id="A21">Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA</nlm:aff></affiliation></author><author><name sortKey="Zikan, Michal" sort="Zikan, Michal" uniqKey="Zikan M" first="Michal" last="Zikan">Michal Zikan</name><affiliation><nlm:aff id="A22">Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic</nlm:aff></affiliation></author><author><name sortKey="Claes, Kathleen" sort="Claes, Kathleen" uniqKey="Claes K" first="Kathleen" last="Claes">Kathleen Claes</name><affiliation><nlm:aff id="A23">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Poppe, Bruce" sort="Poppe, Bruce" uniqKey="Poppe B" first="Bruce" last="Poppe">Bruce Poppe</name><affiliation><nlm:aff id="A23">Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</nlm:aff></affiliation></author><author><name sortKey="Foretova, Lenka" sort="Foretova, Lenka" uniqKey="Foretova L" first="Lenka" last="Foretova">Lenka Foretova</name><affiliation><nlm:aff id="A24">Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic</nlm:aff></affiliation></author><author><name sortKey="Mai, Phuong L" sort="Mai, Phuong L" uniqKey="Mai P" first="Phuong L." last="Mai">Phuong L. Mai</name><affiliation><nlm:aff id="A25">Clinical Genetics Branch, US National Cancer Institute, Rockville, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Greene, Mark H" sort="Greene, Mark H" uniqKey="Greene M" first="Mark H." last="Greene">Mark H. Greene</name><affiliation><nlm:aff id="A25">Clinical Genetics Branch, US National Cancer Institute, Rockville, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Rennert, Gad" sort="Rennert, Gad" uniqKey="Rennert G" first="Gad" last="Rennert">Gad Rennert</name><affiliation><nlm:aff id="A26">Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel</nlm:aff></affiliation></author><author><name sortKey="Lejbkowicz, Flavio" sort="Lejbkowicz, Flavio" uniqKey="Lejbkowicz F" first="Flavio" last="Lejbkowicz">Flavio Lejbkowicz</name><affiliation><nlm:aff id="A26">Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel</nlm:aff></affiliation></author><author><name sortKey="Glendon, Gord" sort="Glendon, Gord" uniqKey="Glendon G" first="Gord" last="Glendon">Gord Glendon</name><affiliation><nlm:aff id="A27">Ontario Cancer Genetics Network (OCGN), Cancer Care Ontario</nlm:aff></affiliation></author><author><name sortKey="Ozcelik, Hilmi" sort="Ozcelik, Hilmi" uniqKey="Ozcelik H" first="Hilmi" last="Ozcelik">Hilmi Ozcelik</name><affiliation><nlm:aff id="A28">Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada</nlm:aff></affiliation></author><author><name sortKey="Andrulis, Irene L" sort="Andrulis, Irene L" uniqKey="Andrulis I" first="Irene L." last="Andrulis">Irene L. Andrulis</name><affiliation><nlm:aff id="A27">Ontario Cancer Genetics Network (OCGN), Cancer Care Ontario</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada</nlm:aff></affiliation></author></analytic><series><title level="j">Cancer research</title><idno type="ISSN">0008-5472</idno><idno type="eISSN">1538-7445</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">The known breast cancer (BC) susceptibility polymorphisms in <italic>FGFR2, TNRC9/TOX3, MAP3K1,LSP1</italic> and 2q35 confer increased risks of BC for <italic>BRCA1</italic> or <italic>BRCA2</italic> mutation carriers. We evaluated the associations of three additional SNPs, rs4973768 in <italic>SLC4A7/NEK10</italic>, rs6504950 in <italic>STXBP4/COX11</italic> and rs10941679 at 5p12 and reanalyzed the previous associations using additional carriers in a sample of 12,525 <italic>BRCA1</italic> and 7,409 <italic>BRCA2</italic> carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased BC risk for <italic>BRCA2</italic> carriers (per-allele Hazard Ratio (HR)=1.10, 95%CI:1.03-1.18, p=0.006 and HR=1.09, 95%CI:1.01-1.19, p=0.03, respectively). Neither SNP was associated with BC risk for <italic>BRCA1</italic> carriers and rs6504950 was not associated with BC for either <italic>BRCA1</italic> or <italic>BRCA2</italic> carriers. Of the nine polymorphisms investigated, seven were associated with BC for <italic>BRCA2</italic> carriers (<italic>FGFR2, TOX3, MAP3K1, LSP1</italic>, 2q35, <italic>SLC4A7</italic>, 5p12, p-values:7×10<sup>−11</sup>-0.03), but only <italic>TOX3</italic> and 2q35 were associated with the risk for <italic>BRCA1</italic> carriers (p=0.0049, 0.03 respectively). All risk associated polymorphisms appear to interact multiplicatively on BC risk for mutation carriers. Based on the joint genotype distribution of the seven risk associated SNPs in <italic>BRCA2</italic> mutation carriers, the 5% of <italic>BRCA2</italic> carriers at highest risk (i.e. between 95<sup>th</sup> and 100<sup>th</sup> percentiles) were predicted to have a probability between 80% and 96% of developing BC by age 80, compared with 42-50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences may be sufficient to influence the clinical management of mutation carriers.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">2984705R</journal-id><journal-id journal-id-type="pubmed-jr-id">2786</journal-id><journal-id journal-id-type="nlm-ta">Cancer Res</journal-id><journal-id journal-id-type="iso-abbrev">Cancer Res.</journal-id><journal-title-group><journal-title>Cancer research</journal-title></journal-title-group><issn pub-type="ppub">0008-5472</issn><issn pub-type="epub">1538-7445</issn></journal-meta><article-meta><article-id pub-id-type="pmid">21118973</article-id><article-id pub-id-type="pmc">2999830</article-id><article-id pub-id-type="doi">10.1158/0008-5472.CAN-10-1907</article-id><article-id pub-id-type="manuscript">UKMS33024</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Common breast cancer susceptibility alleles and the risk of breast cancer for <italic>BRCA1</italic> and <italic>BRCA2</italic> mutation carriers: 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ref-type="aff" rid="A83">83</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Leroux</surname><given-names>Dominique</given-names></name><xref ref-type="aff" rid="A82">82</xref><xref ref-type="aff" rid="A83">83</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Hardouin</surname><given-names>Agnès</given-names></name><xref ref-type="aff" rid="A84">84</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Berthet</surname><given-names>Pascaline</given-names></name><xref ref-type="aff" rid="A84">84</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Faivre</surname><given-names>Laurence</given-names></name><xref ref-type="aff" rid="A85">85</xref><xref ref-type="aff" rid="A86">86</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Loustalot</surname><given-names>Catherine</given-names></name><xref ref-type="aff" rid="A86">86</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Noguchi</surname><given-names>Tetsuro</given-names></name><xref ref-type="aff" rid="A87">87</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Sobol</surname><given-names>Hagay</given-names></name><xref ref-type="aff" rid="A87">87</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Rouleau</surname><given-names>Etienne</given-names></name><xref ref-type="aff" rid="A88">88</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Nogues</surname><given-names>Catherine</given-names></name><xref ref-type="aff" rid="A89">89</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Frénay</surname><given-names>Marc</given-names></name><xref ref-type="aff" rid="A90">90</xref><xref ref-type="aff" rid="A92">92</xref></contrib><contrib contrib-type="author"><name><surname>Vénat-Bouvet</surname><given-names>Laurence</given-names></name><xref ref-type="aff" rid="A91">91</xref><xref ref-type="aff" rid="A92">92</xref></contrib><on-behalf-of>for GEMO</on-behalf-of><xref ref-type="aff" rid="A92">92</xref></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Hopper</surname><given-names>John L.</given-names></name><xref ref-type="aff" rid="A93">93</xref><xref ref-type="aff" rid="A137">137</xref></contrib><contrib contrib-type="author"><name><surname>Daly</surname><given-names>Mary B.</given-names></name><xref ref-type="aff" rid="A77">77</xref><xref ref-type="aff" rid="A137">137</xref></contrib><contrib contrib-type="author"><name><surname>Terry</surname><given-names>Mary B.</given-names></name><xref ref-type="aff" rid="A94">94</xref><xref ref-type="aff" rid="A137">137</xref></contrib><contrib contrib-type="author"><name><surname>John</surname><given-names>Esther M.</given-names></name><xref ref-type="aff" rid="A95">95</xref><xref ref-type="aff" rid="A137">137</xref></contrib><contrib contrib-type="author"><name><surname>Buys</surname><given-names>Saundra S.</given-names></name><xref ref-type="aff" rid="A96">96</xref><xref ref-type="aff" rid="A137">137</xref></contrib><contrib contrib-type="author"><name><surname>Yassin</surname><given-names>Yosuf</given-names></name><xref ref-type="aff" rid="A97">97</xref><xref ref-type="aff" rid="A137">137</xref></contrib><contrib contrib-type="author"><name><surname>Miron</surname><given-names>Alex</given-names></name><xref ref-type="aff" rid="A97">97</xref><xref ref-type="aff" rid="A137">137</xref></contrib><contrib contrib-type="author"><name><surname>Goldgar</surname><given-names>David</given-names></name><xref ref-type="aff" rid="A98">98</xref><xref ref-type="aff" rid="A137">137</xref></contrib><on-behalf-of>for the Breast Cancer Family Registry</on-behalf-of><xref ref-type="aff" rid="A137">137</xref></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Singer</surname><given-names>Christian F.</given-names></name><xref ref-type="aff" rid="A99">99</xref></contrib><contrib contrib-type="author"><name><surname>Dressler</surname><given-names>Anne Catharina</given-names></name><xref ref-type="aff" rid="A99">99</xref></contrib><contrib contrib-type="author"><name><surname>Gschwantler-Kaulich</surname><given-names>Daphne</given-names></name><xref ref-type="aff" rid="A99">99</xref></contrib><contrib contrib-type="author"><name><surname>Pfeiler</surname><given-names>Georg</given-names></name><xref ref-type="aff" rid="A99">99</xref></contrib><contrib contrib-type="author"><name><surname>Hansen</surname><given-names>Thomas V. O.</given-names></name><xref ref-type="aff" rid="A100">100</xref></contrib><contrib contrib-type="author"><name><surname>Jønson</surname><given-names>Lars</given-names></name><xref ref-type="aff" rid="A100">100</xref></contrib><contrib contrib-type="author"><name><surname>Agnarsson</surname><given-names>Bjarni A.</given-names></name><xref ref-type="aff" rid="A101">101</xref></contrib><contrib contrib-type="author"><name><surname>Kirchhoff</surname><given-names>Tomas</given-names></name><xref ref-type="aff" rid="A102">102</xref></contrib><contrib contrib-type="author"><name><surname>Offit</surname><given-names>Kenneth</given-names></name></contrib><contrib contrib-type="author"><name><surname>Devlin</surname><given-names>Vincent</given-names></name><xref ref-type="aff" rid="A102">102</xref></contrib><contrib contrib-type="author"><name><surname>Dutra-Clarke</surname><given-names>Ana</given-names></name><xref ref-type="aff" rid="A102">102</xref></contrib><contrib contrib-type="author"><name><surname>Piedmonte</surname><given-names>Marion</given-names></name><xref ref-type="aff" rid="A103">103</xref></contrib><contrib contrib-type="author"><name><surname>Rodriguez</surname><given-names>Gustavo C.</given-names></name><xref ref-type="aff" rid="A104">104</xref></contrib><contrib contrib-type="author"><name><surname>Wakeley</surname><given-names>Katie</given-names></name><xref ref-type="aff" rid="A105">105</xref></contrib><contrib contrib-type="author"><name><surname>Boggess</surname><given-names>John F.</given-names></name><xref ref-type="aff" rid="A106">106</xref></contrib><contrib contrib-type="author"><name><surname>Basil</surname><given-names>Jack</given-names></name><xref ref-type="aff" rid="A107">107</xref></contrib><contrib contrib-type="author"><name><surname>Schwartz</surname><given-names>Peter E.</given-names></name><xref ref-type="aff" rid="A108">108</xref></contrib><contrib contrib-type="author"><name><surname>Blank</surname><given-names>Stephanie V.</given-names></name><xref ref-type="aff" rid="A109">109</xref></contrib><contrib contrib-type="author"><name><surname>Toland</surname><given-names>Amanda Ewart</given-names></name><xref ref-type="aff" rid="A110">110</xref></contrib><contrib contrib-type="author"><name><surname>Montagna</surname><given-names>Marco</given-names></name><xref ref-type="aff" rid="A111">111</xref></contrib><contrib contrib-type="author"><name><surname>Casella</surname><given-names>Cinzia</given-names></name><xref ref-type="aff" rid="A111">111</xref></contrib><contrib contrib-type="author"><name><surname>Imyanitov</surname><given-names>Evgeny</given-names></name><xref ref-type="aff" rid="A112">112</xref></contrib><contrib contrib-type="author"><name><surname>Tihomirova</surname><given-names>Laima</given-names></name><xref ref-type="aff" rid="A113">113</xref></contrib><contrib contrib-type="author"><name><surname>Blanco</surname><given-names>Ignacio</given-names></name><xref ref-type="aff" rid="A114">114</xref></contrib><contrib contrib-type="author"><name><surname>Lazaro</surname><given-names>Conxi</given-names></name><xref ref-type="aff" rid="A114">114</xref></contrib><contrib contrib-type="author"><name><surname>Ramus</surname><given-names>Susan J.</given-names></name><xref ref-type="aff" rid="A115">115</xref></contrib><contrib contrib-type="author"><name><surname>Sucheston</surname><given-names>Lara</given-names></name><xref ref-type="aff" rid="A116">116</xref></contrib><contrib contrib-type="author"><name><surname>Karlan</surname><given-names>Beth Y.</given-names></name><xref ref-type="aff" rid="A117">117</xref></contrib><contrib contrib-type="author"><name><surname>Gross</surname><given-names>Jenny</given-names></name><xref ref-type="aff" rid="A117">117</xref></contrib><contrib contrib-type="author"><name><surname>Schmutzler</surname><given-names>Rita</given-names></name><xref ref-type="aff" rid="A118">118</xref></contrib><contrib contrib-type="author"><name><surname>Wappenschmidt</surname><given-names>Barbara</given-names></name><xref ref-type="aff" rid="A118">118</xref></contrib><contrib contrib-type="author"><name><surname>Engel</surname><given-names>Christoph</given-names></name><xref ref-type="aff" rid="A119">119</xref></contrib><contrib contrib-type="author"><name><surname>Meindl</surname><given-names>Alfons</given-names></name><xref ref-type="aff" rid="A120">120</xref></contrib><contrib contrib-type="author"><name><surname>Lochmann</surname><given-names>Magdalena</given-names></name><xref ref-type="aff" rid="A121">121</xref></contrib><contrib contrib-type="author"><name><surname>Arnold</surname><given-names>Norbert</given-names></name><xref ref-type="aff" rid="A122">122</xref></contrib><contrib contrib-type="author"><name><surname>Heidemann</surname><given-names>Simone</given-names></name><xref ref-type="aff" rid="A123">123</xref></contrib><contrib contrib-type="author"><name><surname>Varon-Mateeva</surname><given-names>Raymonda</given-names></name><xref ref-type="aff" rid="A124">124</xref></contrib><contrib contrib-type="author"><name><surname>Niederacher</surname><given-names>Dieter</given-names></name><xref ref-type="aff" rid="A125">125</xref></contrib><contrib contrib-type="author"><name><surname>Sutter</surname><given-names>Christian</given-names></name><xref ref-type="aff" rid="A126">126</xref></contrib><contrib contrib-type="author"><name><surname>Deissler</surname><given-names>Helmut</given-names></name><xref ref-type="aff" rid="A127">127</xref></contrib><contrib contrib-type="author"><name><surname>Gadzicki</surname><given-names>Dorothea</given-names></name><xref ref-type="aff" rid="A128">128</xref></contrib><contrib contrib-type="author"><name><surname>Preisler-Adams</surname><given-names>Sabine</given-names></name><xref ref-type="aff" rid="A129">129</xref></contrib><contrib contrib-type="author"><name><surname>Kast</surname><given-names>Karin</given-names></name><xref ref-type="aff" rid="A130">130</xref></contrib><contrib contrib-type="author"><name><surname>Schönbuchner</surname><given-names>Ines</given-names></name><xref ref-type="aff" rid="A131">131</xref></contrib><contrib contrib-type="author"><name><surname>Caldes</surname><given-names>Trinidad</given-names></name><xref ref-type="aff" rid="A132">132</xref></contrib><contrib contrib-type="author"><name><surname>de la Hoya</surname><given-names>Miguel</given-names></name><xref ref-type="aff" rid="A132">132</xref></contrib><contrib contrib-type="author"><name><surname>Aittomäki</surname><given-names>Kristiina</given-names></name><xref ref-type="aff" rid="A133">133</xref></contrib><contrib contrib-type="author"><name><surname>Nevanlinna</surname><given-names>Heli</given-names></name><xref ref-type="aff" rid="A133">133</xref></contrib><contrib contrib-type="author"><name><surname>Simard</surname><given-names>Jacques</given-names></name><xref ref-type="aff" rid="A134">134</xref></contrib><contrib contrib-type="author"><name><surname>Spurdle</surname><given-names>Amanda B.</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A135">135</xref></contrib><contrib contrib-type="author"><name><surname>Holland</surname><given-names>Helene</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A135">135</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Xiaoqing</given-names></name><xref ref-type="aff" rid="A2">2</xref><xref ref-type="aff" rid="A135">135</xref></contrib><on-behalf-of>for kConFab</on-behalf-of><xref ref-type="aff" rid="A135">135</xref></contrib-group><contrib-group><contrib contrib-type="author"><name><surname>Platte</surname><given-names>Radka</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chenevix-Trench</surname><given-names>Georgia</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Easton</surname><given-names>Douglas F.</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><on-behalf-of>on behalf of CIMBA</on-behalf-of></contrib-group><aff id="A1"><label>1</label>Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, UK</aff><aff id="A2"><label>2</label>Queensland Institute of Medical Research; Brisbane, Australia</aff><aff id="A3"><label>3</label>Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Hospitalier Universitaire de Lyon / Centre Léon Bérard, Lyon, France;</aff><aff id="A4"><label>4</label>Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA USA</aff><aff id="A5"><label>5</label>Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania School of Medicine, Philadelphia, PA</aff><aff id="A6"><label>6</label>City of Hope National Medical Center, Duarte, CA</aff><aff id="A7"><label>7</label>Creighton University, Omaha, NE</aff><aff id="A8"><label>8</label>Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC</aff><aff id="A9"><label>9</label>Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, CA</aff><aff id="A10"><label>10</label>University of Texas Health Science Center, San Antonio, TX</aff><aff id="A11"><label>11</label>University of Chicago Medical Center, Chicago, IL</aff><aff id="A12"><label>12</label>Department of Laboratory Medicine and Pathology, Mayo Clinic, Minnesota, USA</aff><aff id="A13"><label>13</label>Department of Medical Genetics, Mayo Clinic, Minnesota, USA</aff><aff id="A14"><label>14</label>Department of Health Sciences Research, Mayo Clinic, Minnesota, USA</aff><aff id="A15"><label>15</label>Unit of Genetic Susceptibility to Cancer, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy and IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.</aff><aff id="A16"><label>16</label>Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy.</aff><aff id="A17"><label>17</label>Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy</aff><aff id="A18"><label>18</label>Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano (PN), Italy.</aff><aff id="A19"><label>19</label>Department of Genetics, Biology and Biochemestry, University of Turin, Turin, Italy</aff><aff id="A20"><label>20</label>Cogentech, Consortium for Genomics Technology, Milan, Italy</aff><aff id="A21"><label>21</label>Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA</aff><aff id="A22"><label>22</label>Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic</aff><aff id="A23"><label>23</label>Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium</aff><aff id="A24"><label>24</label>Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic</aff><aff id="A25"><label>25</label>Clinical Genetics Branch, US National Cancer Institute, Rockville, MD, USA</aff><aff id="A26"><label>26</label>Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel</aff><aff id="A27"><label>27</label>Ontario Cancer Genetics Network (OCGN), Cancer Care Ontario</aff><aff id="A28"><label>28</label>Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital</aff><aff id="A29"><label>29</label>Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada</aff><aff id="A30"><label>30</label>Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada</aff><aff id="A31"><label>31</label>Odense University Hospital, Department of Clinical Genetics, Denmark</aff><aff id="A32"><label>32</label>Department of Clinical Genetics, Rigshospitalet and Odense University Hospital, Denmark,</aff><aff id="A33"><label>33</label>Department of Clinical Genetics, Aalborg Hospital, Denmark,</aff><aff id="A34"><label>34</label>Department of Clinical Genetics, Vejle Hospital, Denmark,</aff><aff id="A35"><label>35</label>Department of Clinical Genetics, Aarhus University Hospital, Denmark</aff><aff id="A36"><label>36</label>Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa and Pisa University Hospital, Pisa, Italy</aff><aff id="A37"><label>37</label>The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical center, Tel-Hashomer, Israel.</aff><aff id="A38"><label>38</label>Oncology Institute, Sheba Medical Center, Tel-Hashomer, Israel.</aff><aff id="A39"><label>39</label>Dept of Oncology, Lund University, S-22185 Lund, Sweden</aff><aff id="A40"><label>40</label>Dept Molecular Medicine and Surgery, Karolinska Insitutet, S17176 Stockholm, Sweden</aff><aff id="A41"><label>41</label>Dept Oncology, Linköping University, S-58185 Linköping, Sweden</aff><aff id="A42"><label>42</label>Dept of Radiation Sciences, Oncology, Umeå University, S-90185 Umeå, Sweden</aff><aff id="A43"><label>43</label>Swedish Breast Cancer Study, Sweden</aff><aff id="A44"><label>44</label>University of Pennsylvania</aff><aff id="A45"><label>45</label>International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland;</aff><aff id="A46"><label>46</label>Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center, Madrid, Spain</aff><aff id="A47"><label>47</label>Genetics Service, Hospital de la Sant Creu i Sant Pau, Barcelona, Spain.</aff><aff id="A48"><label>48</label>Institute of Biology and Molecular Genetics. Universidad de Valladolid (IBGM-UVA), Valladolid, Spain.</aff><aff id="A49"><label>49</label>Molecular Genetics Laboratory (Department of Biochemistry), Cruces Hospital Barakaldo, Bizkaia, Spain</aff><aff id="A50"><label>50</label>Oncology Service, Hospital clínico universitario Lozano Blesa, Zaragoza, Spain and Instituto Aragones de Ciencias de la Salud (I+CS)</aff><aff id="A51"><label>51</label>Human Genetics Group and Genotyping Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Center, Madrid, Spain</aff><aff id="A52"><label>52</label>Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany</aff><aff id="A53"><label>53</label>Department of Medical Oncology, Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands</aff><aff id="A54"><label>54</label>Hereditary Cancer Clinic, Radboud University, Nijmegen edical Center, Nijmegen, The Netherlands</aff><aff id="A55"><label>55</label>Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands</aff><aff id="A56"><label>56</label>Department Of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</aff><aff id="A57"><label>57</label>Department of Human Genetics Department of Pathology, Leiden University Medical Center, Leiden</aff><aff id="A58"><label>58</label>Department of Clinical Genetics, VU Medical Center, Amsterdam, The Netherlands</aff><aff id="A59"><label>59</label>Department of Genetics and Cell Biology, University Medical Center, Maastricht, The Netherlands</aff><aff id="A60"><label>60</label>Department of Clinical Genetics, Academic Medical Center, Amsterdam, Amsterdam, The Netherlands</aff><aff id="A61"><label>61</label>Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands</aff><aff id="A62"><label>62</label>Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands</aff><aff id="A63"><label>63</label>HEereditary Breast and Ovarian cancer group Netherlands (HEBON)</aff><aff id="A64"><label>64</label>Department of Oncology, University of Cambridge, UK</aff><aff id="A65"><label>65</label>Genetic Medicine, Manchester Academic Health Sciences Center, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK</aff><aff id="A66"><label>66</label>Clinical Genetics, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK</aff><aff id="A67"><label>67</label>Ferguson-Smith Center for Clinical Genetics, Glasgow, UK</aff><aff id="A68"><label>68</label>West Midlands Regional Genetics Service, Birmingham Women’s Hospital Healthcare NHS Trust, Edgbaston, Birmingham, UK</aff><aff id="A69"><label>69</label>Sheffield Clinical Genetics Service, Sheffield Children’s Hospital, Sheffield, UK</aff><aff id="A70"><label>70</label>Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, UK</aff><aff id="A71"><label>71</label>Clincal Genetics Department, St Georges Hospital, University of London, UK</aff><aff id="A72"><label>72</label>Northern Ireland Regional Genetics Center, Belfast City Hospital, Belfast, UK</aff><aff id="A73"><label>73</label>South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, UK</aff><aff id="A74"><label>74</label>Oxford Regional Genetics Service, Churchill Hospital, Oxford</aff><aff id="A75"><label>75</label>Cancer Genetics Program, Hope Directorate, St James’s Hospital, Ireland</aff><aff id="A76"><label>76</label>North West Thames Regional Genetics Service, Kennedy-Galton Center, Harrow, UK</aff><aff id="A77"><label>77</label>Women’s Cancer Program, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA USA</aff><aff id="A78"><label>78</label>INSERM U509, Service de Génétique Oncologique, Institut Curie, Université Paris-Descartes, Paris, France</aff><aff id="A79"><label>79</label>Equipe labellisée LIGUE 2008, UMR5201 CNRS, Centre Léon Bérard, Université de Lyon, Lyon, France</aff><aff id="A80"><label>80</label>CNRS UMR5558, Université Lyon 1, Lyon, France</aff><aff id="A81"><label>81</label>Unité de Prévention et d’Epidémiologie Génétique, Centre Léon Bérard, Lyon, France</aff><aff id="A82"><label>82</label>Department of Genetics, Centre Hospitalier Universitaire de Grenoble, Grenoble, France</aff><aff id="A83"><label>83</label>Institut Albert Bonniot, Université de Grenoble, Grenoble, France</aff><aff id="A84"><label>84</label>Centre François Baclesse, Caen, France</aff><aff id="A85"><label>85</label>Centre de Génétique, Centre Hospitalier Universitaire de Dijon, France</aff><aff id="A86"><label>86</label>Centre de Lutte Contre le Cancer Georges François Leclerc, Dijon, France</aff><aff id="A87"><label>87</label>INSERM UMR599, Département d’Oncologie Génétique, Institut Paoli-Calmettes, Marseille, France</aff><aff id="A88"><label>88</label>INSERM U735, Centre René Huguenin, Saint-Cloud, France</aff><aff id="A89"><label>89</label>Epidémiologie Clinique, Oncogénétique, Centre René Huguenin, Saint-Cloud, France</aff><aff id="A90"><label>90</label>Centre Antoine Lacassagne, Nice, France</aff><aff id="A91"><label>91</label>Departement of Oncology, Centre Hospitalier Universitaire de Limoges, Limoges, France</aff><aff id="A92"><label>92</label>GEMO study: Cancer Genetics Network “Groupe Génétique et Cancer”, Fédération Nationale des Centres de Lutte Contre le Cancer, France</aff><aff id="A93"><label>93</label>The University of Melbourne, Melbourne, Australia</aff><aff id="A94"><label>94</label>Columbia University New York, USA</aff><aff id="A95"><label>95</label>Cancer Prevention Institute of California (formerly the Northern California Cancer Center), Fremont and Stanford University School of Medicine, Stanford, CA, USA</aff><aff id="A96"><label>96</label>Huntsman Cancer Institute, University of Utah Health Sciences Centre, Salt Lake City, UT, USA</aff><aff id="A97"><label>97</label>Dana-Farber Cancer Institute, Boston, MA, USA</aff><aff id="A98"><label>98</label>Department of Dermatology, University of Utah, USA</aff><aff id="A99"><label>99</label>Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria</aff><aff id="A100"><label>100</label>Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark</aff><aff id="A101"><label>101</label>Department of Pathology, University Hospital & University of Iceland School of Medicine, Reykjavik, Iceland</aff><aff id="A102"><label>102</label>Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA</aff><aff id="A103"><label>103</label>GOG Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263;</aff><aff id="A104"><label>104</label>NorthShore University Health System, Evanston Northwestern Healthcare, Evanston, IL 60201;</aff><aff id="A105"><label>105</label>Tufts University, New England Medical Center, Boston, MA 02111;</aff><aff id="A106"><label>106</label>University of North Carolina, Chapel Hill, NC 27599;</aff><aff id="A107"><label>107</label>St. Elizabeth Medical Center, Edgewood, KY 41017</aff><aff id="A108"><label>108</label>Yale University School of Medicine, New Haven, CT 06510;</aff><aff id="A109"><label>109</label>New York University School of Medicine, New York, NY 10016;</aff><aff id="A110"><label>110</label>Departments of Internal Medicine and Molecular Virology, Immunology and Medical Genetics, Division of Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA</aff><aff id="A111"><label>111</label>Istituto Oncologico Veneto - IRCCS, Immunology and Molecular Oncology Unit, Padua, Italy</aff><aff id="A112"><label>112</label>N.N. Petrov Institute of Oncology, St.-Petersburg, 197758, Russia</aff><aff id="A113"><label>113</label>Latvian Biomedical Research and Study Center, Riga.</aff><aff id="A114"><label>114</label>Hereditary Cancer Program, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain.</aff><aff id="A115"><label>115</label>Gynaecological Oncology Unit, UCL EGA Institute for Women’s Health, University College London, UK</aff><aff id="A116"><label>116</label>Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263</aff><aff id="A117"><label>117</label>Women’s Cancer Research Institute at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.</aff><aff id="A118"><label>118</label>Center of Familial Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology and Center for Integrated Oncology (CIO), University of Cologne, Germany</aff><aff id="A119"><label>119</label>Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Germany</aff><aff id="A120"><label>120</label>Department of Obstetrics and Gynaecology, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Germany</aff><aff id="A121"><label>121</label>Department of Obstetrics and Gynaecology, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Germany</aff><aff id="A122"><label>122</label>Department of Obstetrics and Gynaecology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Germany</aff><aff id="A123"><label>123</label>Institute of Human Genetics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Germany</aff><aff id="A124"><label>124</label>Institute of Human Genetics, Campus Virchow Klinikum, Charite Berlin, Germany</aff><aff id="A125"><label>125</label>Department of Obstetrics and Gynaecology, Division of Molecular Genetics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Germany</aff><aff id="A126"><label>126</label>Institute of Human Genetics, Division of Molecular Diagnostics, University Heidelberg, Germany</aff><aff id="A127"><label>127</label>Department of Obstetrics and Gynaecology, University Hospital Ulm, Germany,</aff><aff id="A128"><label>128</label>Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany</aff><aff id="A129"><label>129</label>Institute of Human Genetics, University Hospital Muenster, Germany</aff><aff id="A130"><label>130</label>Department of Obstetrics and Gynaecology, University Hospital Carl Gustav Carus, Technical University Dresden, Germany</aff><aff id="A131"><label>131</label>Institute of Human Genetics, Division of Medical Genetics, University Wuerzburg, Germany</aff><aff id="A132"><label>132</label>Molecular oncology laboratory, Hospital Clinico San Carlos, Madrid, Spain</aff><aff id="A133"><label>133</label>Departments of Obstetrics and Gynecology (HN) and Clinical Genetics (KA), Helsinki University Central Hospital, Helsinki, Finl</aff><aff id="A134"><label>134</label>Canada Research Chair in Oncogenetics, Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec, Canada</aff><aff id="A135"><label>135</label>Kathleen Cuningham Consortium for Research into Familial Breast Cancer – Peter MacCallum Cancer Center, Melbourne, Australia</aff><aff id="A136"><label>136</label>Epidemiological study of<italic>BRCA1</italic> and<italic>BRCA2</italic> mutation carriers</aff><aff id="A137"><label>137</label>Breast Cancer Family Registry</aff><author-notes><corresp id="CR1">Corresponding author: Antonis C Antoniou, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN <email>antonis@srl.cam.ac.uk</email>, Tel: +44 1223 740163, Fax: +44 1223 740159</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>28</day><month>10</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>30</day><month>11</month><year>2010</year></pub-date><pub-date pub-type="ppub"><day>1</day><month>12</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>6</month><year>2011</year></pub-date><volume>70</volume><issue>23</issue><fpage>9742</fpage><lpage>9754</lpage><abstract><p id="P1">The known breast cancer (BC) susceptibility polymorphisms in <italic>FGFR2, TNRC9/TOX3, MAP3K1,LSP1</italic> and 2q35 confer increased risks of BC for <italic>BRCA1</italic> or <italic>BRCA2</italic> mutation carriers. We evaluated the associations of three additional SNPs, rs4973768 in <italic>SLC4A7/NEK10</italic>, rs6504950 in <italic>STXBP4/COX11</italic> and rs10941679 at 5p12 and reanalyzed the previous associations using additional carriers in a sample of 12,525 <italic>BRCA1</italic> and 7,409 <italic>BRCA2</italic> carriers. Additionally, we investigated potential interactions between SNPs and assessed the implications for risk prediction. The minor alleles of rs4973768 and rs10941679 were associated with increased BC risk for <italic>BRCA2</italic> carriers (per-allele Hazard Ratio (HR)=1.10, 95%CI:1.03-1.18, p=0.006 and HR=1.09, 95%CI:1.01-1.19, p=0.03, respectively). Neither SNP was associated with BC risk for <italic>BRCA1</italic> carriers and rs6504950 was not associated with BC for either <italic>BRCA1</italic> or <italic>BRCA2</italic> carriers. Of the nine polymorphisms investigated, seven were associated with BC for <italic>BRCA2</italic> carriers (<italic>FGFR2, TOX3, MAP3K1, LSP1</italic>, 2q35, <italic>SLC4A7</italic>, 5p12, p-values:7×10<sup>−11</sup>-0.03), but only <italic>TOX3</italic> and 2q35 were associated with the risk for <italic>BRCA1</italic> carriers (p=0.0049, 0.03 respectively). All risk associated polymorphisms appear to interact multiplicatively on BC risk for mutation carriers. Based on the joint genotype distribution of the seven risk associated SNPs in <italic>BRCA2</italic> mutation carriers, the 5% of <italic>BRCA2</italic> carriers at highest risk (i.e. between 95<sup>th</sup> and 100<sup>th</sup> percentiles) were predicted to have a probability between 80% and 96% of developing BC by age 80, compared with 42-50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences may be sufficient to influence the clinical management of mutation carriers.</p></abstract><kwd-group><kwd><italic>BRCA1</italic></kwd><kwd><italic>BRCA2</italic></kwd><kwd>genetic modifier</kwd><kwd>common variant</kwd><kwd>genome-wide association study</kwd><kwd>penetrance</kwd><kwd>genetic counseling</kwd></kwd-group><funding-group><award-group><funding-source country="United Kingdom">Cancer Research UK : </funding-source><award-id>A11174 || CRUK_</award-id></award-group></funding-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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