Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction
By: Antoniou AC, Beesley J, McGuffog L, Sinilnikova OM, Healey S, Neuhausen SL, Ding YC, Rebbeck TR, Weitzel JN, Lynch HT, Isaacs C, Ganz PA, Tomlinson G, Olopade OI, Couch FJ, Wang X, Lindor NM, Pankratz VS, Radice P, Manoukian S, Peissel B, Zaffaroni D, Barile M, Viel A, Allavena A, Dall'olio V, Peterlongo P, Szabo CI, Zikan M, Claes K, Poppe B, Foretova L, Mai PL, Greene MH, Rennert G, Lejbkowicz F, Glendon G, Ozcelik H, Andrulis IL; for the Ontario Cancer Genetics Network, Thomassen M, Gerdes AM, Sunde L, Cruger D, Birk Jensen U, Caligo M, Friedman E, Kaufman B, Laitman Y, Milgrom R, Dubrovsky M, Cohen S, Borg A, Jernström H, Lindblom A, Rantala J, Stenmark-Askmalm M, Melin B; for SWE-BRCA, Nathanson K, Domchek S, Jakubowska A, Lubinski J, Huzarski T, Osorio A, Lasa A, Durán M, Tejada MI, Godino J, Benitez J, Hamann U, Kriege M, Hoogerbrugge N, Luijt RB, Asperen CJ, Devilee P, Meijers-Heijboer EJ, Blok MJ, Aalfs CM, Hogervorst F, Rookus M; for HEBON, Cook M, Oliver C, Frost D, Conroy D, Evans DG, Lalloo F, Pichert G, Davidson R, Cole T, Cook J, Paterson J, Hodgson S, Morrison PJ, Porteous ME, Walker L, Kennedy MJ, Dorkins H, Peock S; for EMBRACE, Godwin AK, Stoppa-Lyonnet D, Pauw AD, Mazoyer S, Bonadona V, Lasset C, Dreyfus H, Leroux D, Hardouin A, Berthet P, Faivre L; for GEMO, Loustalot C, Noguchi T, Sobol H, Rouleau E, Nogues C, Frénay M, Vénat-Bouvet L; for GEMO, Hopper JL, Daly MB, Terry MB, John EM, Buys SS, Yassin Y, Miron A, Goldgar D; for the Breast Cancer Family Registry, Singer CF, Dressler AC, Gschwantler-Kaulich D, Pfeiler G, Hansen TV, Jønson L, Agnarsson BA, Kirchhoff T, Offit K, Devlin V, Dutra-Clarke A, Piedmonte M, Rodriguez GC, Wakeley K, Boggess JF, Basil J, Schwartz PE, Blank SV, Toland AE, Montagna M, Casella C, Imyanitov E, Tihomirova L, Blanco I, Lazaro C, Ramus SJ, Sucheston L, Karlan BY, Gross J, Schmutzler R, Wappenschmidt B, Engel C, Meindl A, Lochmann M, Arnold N, Heidemann S, Varon-Mateeva R, Niederacher D, Sutter C, Deissler H, Gadzicki D, Preisler-Adams S, Kast K, Schönbuchner I, Caldes T, Hoya MD, Aittomäki K, Nevanlinna H, Simard J, Spurdle AB, Holland H, Chen X; for kConFab, Platte R, Chenevix-Trench G, Easton DF; on behalf of CIMBA.
Authors' Affiliations: Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Queensland Institute of Medical Research, Brisbane, Australia; Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Hospitalier Universitaire de Lyon/Centre Léon Bérard, Lyon, France; Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, California; Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; City of Hope National Medical Center, Duarte, California; Creighton University, Omaha, Nebraska; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia; Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, California; University of Texas Health Science Center, San Antonio, Texas; University of Chicago Medical Center, Chicago, Illinois; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; 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; Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy; Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano (PN), Italy; Department of Genetics, Biology and Biochemestry, University of Turin, Turin, Italy; Cogentech, Consortium for Genomics Technology, Milan, Italy; Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota; Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium; Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic; Clinical Genetics Branch, US National Cancer Institute, Rockville, Maryland; Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel; Ontario Cancer Genetics Network (OCGN), Cancer Care Ontario, Toronto, Ontario, Canada; Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, New York; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; Odense University Hospital, Department of Clinical Genetics, Odense, Denmark; Department of Clinical Genetics, Rigshospitalet and Odense University Hospital, Odense, Denmark; Department of Clinical Genetics, Aalborg Hospital, Aalborg, Denmark; Department of Clinical Genetics, Vejle Hospital, Velje, Denmark; Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark; Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa and Pisa University Hospital, Pisa, Italy; The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel; Oncology Institute, Sheba Medical Center, Tel-Hashomer, Israel; Department of Oncology, Lund University, Lund, Sweden; Department of Molecular Medicine and Surgery, Karolinska Insitutet, Stockholm, Sweden; Department of Oncology, Linköping University, Linköping, Sweden; Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden; Swedish Breast Cancer Study, Sweden; University of Pennsylvania, Philadelphia, Pennsylvania; International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center, Madrid, Spain; Genetics Service, Hospital de la Sant Creu i Sant Pau, Barcelona, Spain; Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain; Molecular Genetics Laboratory (Department of Biochemistry), Cruces Hospital Barakaldo, Bizkaia, Spain; Oncology Service, Hospital clínico universitario Lozano Blesa, Zaragoza, Spain and Instituto Aragones de Ciencias de la Salud (I+CS); Human Genetics Group and Genotyping Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Center, Madrid, Spain; Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; Department of Medical Oncology, Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Hereditary Cancer Clinic, Radboud University, Nijmegen Medical Center, Nijmegen, the Netherlands; Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands; Department Of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands; Department of Human Genetics, Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Genetics, VU Medical Center, Amsterdam, the Netherlands; Department of Genetics and Cell Biology, University Medical Center, Maastricht, the Netherlands; Department of Clinical Genetics, Academic Medical Center, Amsterdam, Amsterdam, the Netherlands; Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands; HEreditary Breast and Ovarian Cancer Group Netherlands (HEBON); Department of Oncology, University of Cambridge, Cambridge, United Kingdom; Genetic Medicine, Manchester Academic Health Sciences Center, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom; Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom; Ferguson-Smith Center for Clinical Genetics, Glasgow, United Kingdom; West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, United Kingdom; Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, United Kingdom; Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, United Kingdom; Clinical Genetics Department, St Georges Hospital, University of London, London, United Kingdom; Northern Ireland Regional Genetics Center, Belfast City Hospital, Belfast, United Kingdom; South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, United Kingdom; Oxford Regional Genetics Service, Churchill Hospital, Oxford, United Kingdom; Cancer Genetics Program, Hope Directorate, St James's Hospital, Dublin, Ireland; North West Thames Regional Genetics Service, Kennedy-Galton Center, Harrow, United Kingdom; Women's Cancer Program, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; INSERM U509, Service de Génétique Oncologique, Institut Curie, Université Paris-Descartes, Paris, France; Equipe labellisée LIGUE 2008, UMR5201 CNRS, Centre Léon Bérard, Université de Lyon, Lyon, France; CNRS UMR5558, Université Lyon 1, Lyon, France; Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, Lyon, France; Department of Genetics, Centre Hospitalier Universitaire de Grenoble, Grenoble, France; Institut Albert Bonniot, Université de Grenoble, Grenoble, France; Centre François Baclesse, Caen, France; Centre de Génétique, Centre Hospitalier Universitaire de Dijon, Dijon, France; Centre de Lutte Contre le Cancer Georges François Leclerc, Dijon, France; INSERM UMR599, Département d'Oncologie Génétique, Institut Paoli-Calmettes, Marseille, France; INSERM U735, Centre René Huguenin, Saint-Cloud, France; Epidémiologie Clinique, Oncogénétique, Centre René Huguenin, Saint-Cloud, France; Centre Antoine Lacassagne, Nice, France; Departement of Oncology, Centre Hospitalier Universitaire de Limoges, Limoges, France; GEMO study: Cancer Genetics Network "Groupe Génétique et Cancer", Fédération Nationale des Centres de Lutte Contre le Cancer, France; The University of Melbourne, Melbourne, Australia; Columbia University, New York, New York; Cancer Prevention Institute of California (formerly the Northern California Cancer Center), Fremont and Stanford University School of Medicine, Stanford, California; Huntsman Cancer Institute, University of Utah Health Sciences Centre, Salt Lake City, Utah; Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Dermatology, University of Utah, Salt Lake City, Utah; Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria; Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Pathology, University Hospital & University of Iceland School of Medicine, Reykjavik, Iceland; Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; GOG Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York; NorthShore University Health System, Evanston Northwestern Healthcare, Evanston, Illinois; Tufts University, New England Medical Center, Boston, Massachusetts; University of North Carolina, Chapel Hill, North Carolina; St. Elizabeth Medical Center, Edgewood, Kentucky; Yale University School of Medicine, New Haven, Connecticut; New York University School of Medicine, New York, New York; Departments of Internal Medicine and Molecular Virology, Immunology and Medical Genetics, Division of Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio; Istituto Oncologico Veneto-IRCCS, Immunology and Molecular Oncology Unit, Padua, Italy; N.N. Petrov Institute of Oncology, St.-Petersburg, Russia; Latvian Biomedical Research and Study Center, Riga, Latvia; Hereditary Cancer Program, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain; Gynaecological Oncology Unit, UCL EGA Institute for Women's Health, University College London, London, United Kingdom; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York; Women's Cancer Research Institute at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California; Center of Familial Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology and Center for Integrated Oncology (CIO), University of Cologne, Cologne, Germany; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; Department of Obstetrics and Gynaecology, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany; Department of Obstetrics and Gynaecology, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany; Department of Obstetrics and Gynaecology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany; Institute of Human Genetics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany; Institute of Human Genetics, Campus Virchow Klinikum, Charite Berlin, Berlin, Germany; Department of Obstetrics and Gynaecology, Division of Molecular Genetics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany; Institute of Human Genetics, Division of Molecular Diagnostics, University Heidelberg, Heidelberg, Germany; Department of Obstetrics and Gynaecology, University Hospital Ulm, Ulm, Germany; Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany; Institute of Human Genetics, University Hospital Muenster, Muenster, Germany; Department of Obstetrics and Gynaecology, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany; Institute of Human Genetics, Division of Medical Genetics, University Wuerzburg, Wuerzburg, Germany; Molecular Oncology Laboratory, Hospital Clinico San Carlos, Madrid, Spain; Departments of Obstetrics and Gynecology (HN) and Clinical Genetics (KA), Helsinki University Central Hospital, Helsinki, Finland; Canada Research Chair in Oncogenetics, Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec, Canada; Kathleen Cuningham Consortium for Research into Familial Breast Cancer-Peter MacCallum Cancer Center, Melbourne, Australia; Epidemiological study of BRCA1 and BRCA2 mutation carriers; Breast Cancer Family Registry.
Cancer Res. 2010 Nov 30.
Authors' Affiliations: Center for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Queensland Institute of Medical Research, Brisbane, Australia; Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Hospitalier Universitaire de Lyon/Centre Léon Bérard, Lyon, France; Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, California; Abramson Cancer Center and Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; City of Hope National Medical Center, Duarte, California; Creighton University, Omaha, Nebraska; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia; Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, California; University of Texas Health Science Center, San Antonio, Texas; University of Chicago Medical Center, Chicago, Illinois; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota; Department of Medical Genetics, Mayo Clinic, Rochester, Minnesota; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota; 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; Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia (IEO), Milan, Italy; Division of Experimental Oncology 1, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano (PN), Italy; Department of Genetics, Biology and Biochemestry, University of Turin, Turin, Italy; Cogentech, Consortium for Genomics Technology, Milan, Italy; Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota; Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium; Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic; Clinical Genetics Branch, US National Cancer Institute, Rockville, Maryland; Carmel Medical Center and B. Rappaport Faculty of Medicine, Technion, Haifa, Israel; Ontario Cancer Genetics Network (OCGN), Cancer Care Ontario, Toronto, Ontario, Canada; Fred A. Litwin Center for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, New York; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada; Odense University Hospital, Department of Clinical Genetics, Odense, Denmark; Department of Clinical Genetics, Rigshospitalet and Odense University Hospital, Odense, Denmark; Department of Clinical Genetics, Aalborg Hospital, Aalborg, Denmark; Department of Clinical Genetics, Vejle Hospital, Velje, Denmark; Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark; Division of Surgical, Molecular and Ultrastructural Pathology, Department of Oncology, University of Pisa and Pisa University Hospital, Pisa, Italy; The Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel; Oncology Institute, Sheba Medical Center, Tel-Hashomer, Israel; Department of Oncology, Lund University, Lund, Sweden; Department of Molecular Medicine and Surgery, Karolinska Insitutet, Stockholm, Sweden; Department of Oncology, Linköping University, Linköping, Sweden; Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden; Swedish Breast Cancer Study, Sweden; University of Pennsylvania, Philadelphia, Pennsylvania; International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland; Human Genetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center, Madrid, Spain; Genetics Service, Hospital de la Sant Creu i Sant Pau, Barcelona, Spain; Institute of Biology and Molecular Genetics, Universidad de Valladolid (IBGM-UVA), Valladolid, Spain; Molecular Genetics Laboratory (Department of Biochemistry), Cruces Hospital Barakaldo, Bizkaia, Spain; Oncology Service, Hospital clínico universitario Lozano Blesa, Zaragoza, Spain and Instituto Aragones de Ciencias de la Salud (I+CS); Human Genetics Group and Genotyping Unit, Human Cancer Genetics Programme, Spanish National Cancer Research Center, Madrid, Spain; Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany; Department of Medical Oncology, Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, the Netherlands; Hereditary Cancer Clinic, Radboud University, Nijmegen Medical Center, Nijmegen, the Netherlands; Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands; Department Of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands; Department of Human Genetics, Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands; Department of Clinical Genetics, VU Medical Center, Amsterdam, the Netherlands; Department of Genetics and Cell Biology, University Medical Center, Maastricht, the Netherlands; Department of Clinical Genetics, Academic Medical Center, Amsterdam, Amsterdam, the Netherlands; Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, the Netherlands; Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands; HEreditary Breast and Ovarian Cancer Group Netherlands (HEBON); Department of Oncology, University of Cambridge, Cambridge, United Kingdom; Genetic Medicine, Manchester Academic Health Sciences Center, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom; Clinical Genetics, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom; Ferguson-Smith Center for Clinical Genetics, Glasgow, United Kingdom; West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Edgbaston, Birmingham, United Kingdom; Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, United Kingdom; Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrookes Hospital, Cambridge, United Kingdom; Clinical Genetics Department, St Georges Hospital, University of London, London, United Kingdom; Northern Ireland Regional Genetics Center, Belfast City Hospital, Belfast, United Kingdom; South East of Scotland Regional Genetics Service, Western General Hospital, Edinburgh, United Kingdom; Oxford Regional Genetics Service, Churchill Hospital, Oxford, United Kingdom; Cancer Genetics Program, Hope Directorate, St James's Hospital, Dublin, Ireland; North West Thames Regional Genetics Service, Kennedy-Galton Center, Harrow, United Kingdom; Women's Cancer Program, Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania; INSERM U509, Service de Génétique Oncologique, Institut Curie, Université Paris-Descartes, Paris, France; Equipe labellisée LIGUE 2008, UMR5201 CNRS, Centre Léon Bérard, Université de Lyon, Lyon, France; CNRS UMR5558, Université Lyon 1, Lyon, France; Unité de Prévention et d'Epidémiologie Génétique, Centre Léon Bérard, Lyon, France; Department of Genetics, Centre Hospitalier Universitaire de Grenoble, Grenoble, France; Institut Albert Bonniot, Université de Grenoble, Grenoble, France; Centre François Baclesse, Caen, France; Centre de Génétique, Centre Hospitalier Universitaire de Dijon, Dijon, France; Centre de Lutte Contre le Cancer Georges François Leclerc, Dijon, France; INSERM UMR599, Département d'Oncologie Génétique, Institut Paoli-Calmettes, Marseille, France; INSERM U735, Centre René Huguenin, Saint-Cloud, France; Epidémiologie Clinique, Oncogénétique, Centre René Huguenin, Saint-Cloud, France; Centre Antoine Lacassagne, Nice, France; Departement of Oncology, Centre Hospitalier Universitaire de Limoges, Limoges, France; GEMO study: Cancer Genetics Network "Groupe Génétique et Cancer", Fédération Nationale des Centres de Lutte Contre le Cancer, France; The University of Melbourne, Melbourne, Australia; Columbia University, New York, New York; Cancer Prevention Institute of California (formerly the Northern California Cancer Center), Fremont and Stanford University School of Medicine, Stanford, California; Huntsman Cancer Institute, University of Utah Health Sciences Centre, Salt Lake City, Utah; Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Dermatology, University of Utah, Salt Lake City, Utah; Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria; Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Pathology, University Hospital & University of Iceland School of Medicine, Reykjavik, Iceland; Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York; GOG Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York; NorthShore University Health System, Evanston Northwestern Healthcare, Evanston, Illinois; Tufts University, New England Medical Center, Boston, Massachusetts; University of North Carolina, Chapel Hill, North Carolina; St. Elizabeth Medical Center, Edgewood, Kentucky; Yale University School of Medicine, New Haven, Connecticut; New York University School of Medicine, New York, New York; Departments of Internal Medicine and Molecular Virology, Immunology and Medical Genetics, Division of Human Cancer Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio; Istituto Oncologico Veneto-IRCCS, Immunology and Molecular Oncology Unit, Padua, Italy; N.N. Petrov Institute of Oncology, St.-Petersburg, Russia; Latvian Biomedical Research and Study Center, Riga, Latvia; Hereditary Cancer Program, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain; Gynaecological Oncology Unit, UCL EGA Institute for Women's Health, University College London, London, United Kingdom; Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York; Women's Cancer Research Institute at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California; Center of Familial Breast and Ovarian Cancer, Department of Obstetrics and Gynaecology and Center for Integrated Oncology (CIO), University of Cologne, Cologne, Germany; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany; Department of Obstetrics and Gynaecology, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany; Department of Obstetrics and Gynaecology, Division of Tumor Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany; Department of Obstetrics and Gynaecology, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany; Institute of Human Genetics, University Hospital of Schleswig-Holstein, Campus Kiel, Christian-Albrechts University Kiel, Kiel, Germany; Institute of Human Genetics, Campus Virchow Klinikum, Charite Berlin, Berlin, Germany; Department of Obstetrics and Gynaecology, Division of Molecular Genetics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany; Institute of Human Genetics, Division of Molecular Diagnostics, University Heidelberg, Heidelberg, Germany; Department of Obstetrics and Gynaecology, University Hospital Ulm, Ulm, Germany; Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany; Institute of Human Genetics, University Hospital Muenster, Muenster, Germany; Department of Obstetrics and Gynaecology, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany; Institute of Human Genetics, Division of Medical Genetics, University Wuerzburg, Wuerzburg, Germany; Molecular Oncology Laboratory, Hospital Clinico San Carlos, Madrid, Spain; Departments of Obstetrics and Gynecology (HN) and Clinical Genetics (KA), Helsinki University Central Hospital, Helsinki, Finland; Canada Research Chair in Oncogenetics, Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec and Laval University, Quebec, Canada; Kathleen Cuningham Consortium for Research into Familial Breast Cancer-Peter MacCallum Cancer Center, Melbourne, Australia; Epidemiological study of BRCA1 and BRCA2 mutation carriers; Breast Cancer Family Registry.
Cancer Res. 2010 Nov 30.
Abstract
The known breast cancer susceptibility polymorphisms in FGFR2, TNRC9/TOX3, MAP3K1, LSP1, and 2q35 confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. We evaluated the associations of 3 additional single nucleotide polymorphisms (SNPs), rs4973768 in SLC4A7/NEK10, rs6504950 in STXBP4/COX11, and rs10941679 at 5p12, and reanalyzed the previous associations using additional carriers in a sample of 12,525 BRCA1 and 7,409 BRCA2 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 breast cancer risk for BRCA2 carriers (per-allele 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 breast cancer risk for BRCA1 carriers, and rs6504950 was not associated with breast cancer for either BRCA1 or BRCA2 carriers. Of the 9 polymorphisms investigated, 7 were associated with breast cancer for BRCA2 carriers (FGFR2, TOX3, MAP3K1, LSP1, 2q35, SLC4A7, 5p12, P = 7 × 10(-11) - 0.03), but only TOX3 and 2q35 were associated with the risk for BRCA1 carriers (P = 0.0049, 0.03, respectively). All risk-associated polymorphisms appear to interact multiplicatively on breast cancer risk for mutation carriers. Based on the joint genotype distribution of the 7 risk-associated SNPs in BRCA2 mutation carriers, the 5% of BRCA2 carriers at highest risk (i.e., between 95th and 100th percentiles) were predicted to have a probability between 80% and 96% of developing breast cancer by age 80, compared with 42% to 50% for the 5% of carriers at lowest risk. Our findings indicated that these risk differences might be sufficient to influence the clinical management of mutation carriers. Cancer Res; 70(23); 9742-54. ©2010 AACR.
PMID: 21118973 [PubMed - as supplied by publisher] Source: National Library of Medicine.
