An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers.

Autor:	Blein S; INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France. sophie.blein@gmail.com.; Université de Lyon, 69000, Lyon, France. sophie.blein@gmail.com.; Université Lyon 1, 69100, Villeurbanne, France. sophie.blein@gmail.com., Bardel C; Université de Lyon, 69000, Lyon, France. claire.bardel@univ-lyon1.fr.; Université Lyon 1, 69100, Villeurbanne, France. claire.bardel@univ-lyon1.fr.; UMR CNRS 5558, Laboratoire de Biométrie et Biologie Évolutive (LBBE), 'Biométrie et Biologie Évolutive', Université Claude Bernard Lyon 1, Bâtiment Grégor Mendel, 43 boulevard du 11 novembre 1918, 69622, Villeurbanne, cedex, France. claire.bardel@univ-lyon1.fr., Danjean V; Université Grenoble Alpes, UMR 5217, Laboratoire d'Informatique de Grenoble (LIG), équipe-projet Multi-programmation et Ordonnancement sur ressources pour les Applications Interactives de Simulation (MOAIS), 38041, Grenoble, France. vincent.danjean@ens-lyon.org.; INRIA Rhône-Alpes, équipe-projet MOAIS, 38334, Saint Ismier, Cedex, France. vincent.danjean@ens-lyon.org., McGuffog L; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. lesley@srl.cam.ac.uk., Healey S; Department of Genetics and Computational Biology, QIMR Berghofer, Brisbane, Australia. sue.healey@qimrberghofer.edu.au., Barrowdale D; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. daniel@srl.cam.ac.uk., Lee A; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. andrewl@srl.cam.ac.uk., Dennis J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. jgd29@cam.ac.uk., Kuchenbaecker KB; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. karoline@srl.cam.ac.uk., Soucy P; Centre de recherche du Centre hospitalier universitaire de Québec, Laval University, Charlesbourg, PQ, Canada. penny.soucy@crchul.ulaval.ca., Terry MB; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA. mt146@cumc.columbia.edu., Chung WK; Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY, USA. wkc15@columbia.edu.; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA. wkc15@columbia.edu., Goldgar DE; Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT, USA. david.goldgar@hsc.utah.edu., Buys SS; Department of Internal Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA. saundra.buys@hci.utah.edu., Janavicius R; Hematology, Oncology and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania. ramunas.janavicius@santa.lt.; Department of Molecular and Regenerative Medicine, Centre for Innovative Medicine, State Research Institute, Vilnius, Lithuania. ramunas.janavicius@santa.lt., Tihomirova L; Latvian Biomedical Research and Study Centre, Rātsupītes iela 1, Rīga, LV-1067, Latvia. laima@biomed.lu.lv., Tung N; Division of Hematology Oncology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Shapiro 9, Boston, MA, 02215-5400, USA. ntung@bidmc.harvard.edu., Dorfling CM; Department of Genetics, University of Pretoria, Private Bag X20, Hatfield, 0028, Pretoria, South Africa. celmari.dorfling@up.ac.za., van Rensburg EJ; Department of Genetics, University of Pretoria, Private Bag X20, Hatfield, 0028, Pretoria, South Africa. lizette.vanrensburg@up.ac.za., Neuhausen SL; Department of Population Sciences, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. sneuhausen@coh.org., Ding YC; Department of Population Sciences, Beckman Research Institute, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. ycding@coh.org., Gerdes AM; Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. anne-marie.gerdes@regionh.dk., Ejlertsen B; Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. bent.ejlertsen@regionh.dk., Nielsen FC; Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. fcn@rh.dk., Hansen TV; Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. tvoh@rh.dk., Osorio A; Human Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain. aosorio@cnio.es.; Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain. aosorio@cnio.es., Benitez J; Human Genetics Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain. jbenitez@cnio.es.; Center for Biomedical Network Research on Rare Diseases (CIBERER), Madrid, Spain. jbenitez@cnio.es., Conejero RA; Medical Oncology Service, Hospital Clínico Universitario Lozano Blesa, Avenida San Juan Bosco, 15, 50009, Zaragoza, Spain. andresraquel@hotmail.com., Segota E; Holy Cross Hospital, Michael and Dianne Bienes Comprehensive Cancer Center, Fort Lauderdale, FL, USA. zdenka.segota@holy-cross.com.; Clinical Cancer Genetics Community Research Network, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. zdenka.segota@holy-cross.com., Weitzel JN; Division of Clinical Cancer Genetics, City of Hope (for the Clinical Cancer Genetics Community Research Network), City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. jweitzel@coh.org., Thelander M; John Muir Medical Center, Walnut Creek, CA, USA; c/o Clinical Cancer Genetics Community Research Network, City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. margo.thelander@johnmuirhealth.com., Peterlongo P; Istituto FIRC di Oncologia Molecolare (IFOM), Via Adamello 16, 20139, Milan, Italy. paolo.peterlongo@ifom.eu., Radice P; Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milan, Italy. paolo.radice@istitutotumori.mi.it., Pensotti V; Division of Clinical Cancer Genetics, City of Hope (for the Clinical Cancer Genetics Community Research Network), City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA. valeria.pensotti@ifom.eu.; Cogentech Cancer Genetic Test Laboratory, Via Adamello 16, 20139, Milan, Italy. valeria.pensotti@ifom.eu., Dolcetti R; Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico (CRO), Via Franco Gallini 2, 33081, Aviano, Italy. rdolcetti@cro.it., Bonanni B; Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Via Ripamonti 435, 20141, Milan, Italy. bernardo.bonanni@ieo.it., Peissel B; Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milan, Italy. bernard.peissel@istitutotumori.mi.it., Zaffaroni D; Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milan, Italy. daniela.zaffaroni@istitutotumori.mi.it., Scuvera G; Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milan, Italy. giulietta.scuvera@istitutotumori.m.it., Manoukian S; Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale dei Tumori (INT), Via Venezian 1, 20133, Milan, Italy. siranoush.manoukian@istitutotumori.mi.it., Varesco L; Unit of Hereditary Cancer, Department of Epidemiology, Prevention and Special Functions, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Azienda Ospedaliera Universitaria 'San Martino' di Genova, IST Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, 10, 16132, Genoa, Italy. liliana.varesco@hsanmartino.it., Capone GL; FiorGen Foundation for Pharmacogenomics, Via Luigi Sacconi 6, 50019, Sesto Fiorentino, Italy. gabrycapo86@gmail.com.; Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy. gabrycapo86@gmail.com., Papi L; Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy. l.papi@dfc.unifi.it., Ottini L; Department of Molecular Medicine, Sapienza University, Rome, Italy. laura.ottini@uniroma1.it., Yannoukakos D; Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. yannouka@rrp.demokritos.gr., Konstantopoulou I; Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research 'Demokritos', Aghia Paraskevi Attikis, Athens, Greece. reena@rrp.demokritos.gr., Garber J; Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA. judy_garber@dfci.harvard.edu., Hamann U; Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany. u.hamann@dkfz-heidelberg.de., Donaldson A; Clinical Genetics Department, St Michael's Hospital, Southwell Street, Bristol, BS2 8EG, UK. alan.donaldson@uhbristol.nhs.uk., Brady A; North West Thames Regional Genetics Service, Kennedy-Galton Centre, Harrow, UK. a.brady@imperial.ac.uk., Brewer C; Department of Clinical Genetics, Royal Devon & Exeter Hospital, Barrack Road, Exeter, EX2 5DW, UK. carole.brewer1@nhs.net., Foo C; Merseyside and Cheshire Clinical Genetics Service, Liverpool Women's NHS Foundation Trust, Crown Street, Liverpool, Merseyside, L8 7SS, UK. claire.foo@lwh.nhs.uk., Evans DG; Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. gareth.evans@cmft.nhs.uk., Frost D; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Worts Causeway, Cambridge, CB1 8RN, UK. djsf2@medschl.cam.ac.uk., Eccles D; Faculty of Medicine, University of Southampton, Southampton University Hospitals NHS Trust, Mailpoint 801, South Academic Block, PAH/G/MP105, Tremona Road, Southampton, SO16 6YD, UK. d.m.eccles@soton.ac.uk., Douglas F; Institute of Human Genetics, Northern Genetic Service, International Centre for Life, Newcastle upon Tyne Hospitals NHS Trust, Central Parkway, Newcastle upon Tyne, NE1 4EP, UK. fiona.douglas@nuth.nhs.uk., Cook J; Sheffield Clinical Genetics Service, Sheffield Children's Hospital, Sheffield, UK. jackie.cook@sch.nhs.uk., Adlard J; Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Old Medical School, Leeds General Infirmary, Leeds, LS1 3EX, UK. julian.adlard@leedsth.nhs.uk., Barwell J; Leicestershire Clinical Genetics Service, Department of Clinical Genetics, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, LE1 5WW, UK. julian.barwell@uhl-tr.nhs.uk., Walker L; Oxford Regional Genetics Service, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK. lisa.walker@ouh.nhs.uk., Izatt L; Clinical Genetics Service, Guy's and St Thomas' NHS Foundation Trust, 7th floor, Borough Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK. louise.izatt@gstt.nhs.uk., Side LE; North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, Barclay House, 37, Queen Square, London, WC1N 3BH, UK. sidel@gosh.nhs.uk., Kennedy MJ; North East Thames Regional Genetics Service, Great Ormond Street Hospital for Children NHS Trust, Barclay House, 37, Queen Square, London, WC1N 3BH, UK. jkennedy@stjames.ie.; Academic Unit of Clinical and Molecular Oncology, Trinity College Dublin, College Green, Dublin 2, Ireland. jkennedy@stjames.ie.; Medical Oncology Service, St James's Hospital, James's Street, Dublin 8, Ireland. jkennedy@stjames.ie., Tischkowitz M; Department of Clinical Genetics, East Anglian Regional Genetics Service, Addenbrooke's Hospital, Level 6, Addenbrooke's Treatment Centre, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, CB2 0QQ, UK. mdt33@cam.ac.uk., Rogers MT; All Wales Medical Genetics Services, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK. mark.rogers@wales.nhs.uk., Porteous ME; South East Scotland Regional Genetic Service, Western General Hospital, David Brock Building, Crewe Road South, Edinburgh, EH4 2XU, UK. mary.porteous@ed.ac.uk., Morrison PJ; Centre for Cancer Research & Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7AE, UK. patrick.morrison@belfasttrust.hscni.net.; Department of Medical Genetics, Belfast Health and Social Care Trust, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, UK. patrick.morrison@belfasttrust.hscni.net., Platte R; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Worts Causeway, Cambridge, CB1 8RN, UK. rp356@medschl.cam.ac.uk., Eeles R; Oncogenetics Team, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, 123 Old Brompton Road, London, SW7 3RP, UK. rosalind.eeles@icr.ac.uk., Davidson R; Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Block 4, Glasgow, G3 8SJ, UK. rosemarie.davidson@ggc.scot.nhs.uk., Hodgson S; South West Thames Regional Genetics Service, Department of Medical Genetics, St George's University of London, Cranmer Terrace, London, SW17 0RE, UK. shodgson@sgul.ac.uk., Cole T; West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare NHS Trust, Mindelsohn Way, Edgbaston, Birmingham, B15 2TG, UK. trevor.cole@bwhct.nhs.uk., Godwin AK; Department of Pathology & Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, 66160, USA. agodwin@kumc.edu., Isaacs C; Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, 3800 Reservoir Road NW, Washington, DC, 20057, USA. isaacsc@georgetown.edu., Claes K; Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. kathleen.claes@ugent.be., De Leeneer K; Center for Medical Genetics, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium. kim.deleeneer@ugent.be., Meindl A; Division of Tumor Genetics, Department of Gynaecology and Obstetrics, University Hospital Klinikum Rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675, Munich, Germany. alfons.meindl@lrz.tu-muenchen.de., Gehrig A; Center of Familial Breast and Ovarian Cancer, Department of Medical Genetics, Institut für Humangenetik, Biozentrum, Universität Würzburg, Am Hubland, 97074, Würzburg, Germany. gehrig@biozentrum.uni-wuerzburg.de., Wappenschmidt B; Center for Hereditary Breast and Ovarian Cancer, Medical Faculty, Center for Integrated Oncology (CIO) Cancer Center Cologne, University Hospital Cologne, Cologne, Germany. barbara.wappenschmidt@uk-koeln.de.; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Strasse 21, 50931, Cologne, Germany. barbara.wappenschmidt@uk-koeln.de., Sutter C; Department of Human Genetics, Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany. c.sutter@med.uni-heidelberg.de., Engel C; Institute for Medical Informatics, Statistics and Epidemiology, Medical Faculty, University of Leipzig, Leipzig, Germany. christoph.engel@imise.uni-leipzig.de., Niederacher D; Department of Gynaecology and Obstetrics, University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany. niederac@med.uni-duesseldorf.de., Steinemann D; Institute of Cell and Molecular Pathology, Centre for Pathology and Forensic and Genetic Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany. steinemann.doris@mh-hannover.de., Plendl H; Institute of Human Genetics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. plendl@medgen.uni-kiel.de., Kast K; Department of Gynecology and Obstetrics, University Hospital Carl Gustav Carus of Dresden, Technical University Dresden, Dresden, Germany. karin.kast@uniklinikum-dresden.de., Rhiem K; Center for Hereditary Breast and Ovarian Cancer, Medical Faculty, Center for Integrated Oncology (CIO) Cancer Center Cologne, University Hospital Cologne, Cologne, Germany. kerstin.rhiem@uk-koeln.de.; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Strasse 21, 50931, Cologne, Germany. kerstin.rhiem@uk-koeln.de., Ditsch N; Division of Tumor Genetics, Department of Gynaecology and Obstetrics, University Hospital Klinikum Rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675, Munich, Germany. nina.ditsch@med.uni-muenchen.de., Arnold N; Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 3, D-24105, Kiel, Germany. norbert.arnold@uksh.de., Varon-Mateeva R; Institute of Medical Genetics and Human Genetics, Campus Virchow-Klinikum, Charité Berlin - Universtitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. raymonda.varon-mateeva@charite.de., Schmutzler RK; Center for Hereditary Breast and Ovarian Cancer, Medical Faculty, Center for Integrated Oncology (CIO) Cancer Center Cologne, University Hospital Cologne, Cologne, Germany. rita.schmutzler@uk-koeln.de.; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Strasse 21, 50931, Cologne, Germany. rita.schmutzler@uk-koeln.de.; German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC), Cologne, Germany. rita.schmutzler@uk-koeln.de., Preisler-Adams S; Institute of Human Genetics, University Hospital Münster, Vesaliusweg 12-14, 48149, Münster, Germany., Markov NB; Institute of Human Genetics, University Hospital Münster, Vesaliusweg 12-14, 48149, Münster, Germany. nadja.bogdanova-markov@ukmuenster.de., Wang-Gohrke S; Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, Germany. shan.wang-gohrke@uniklinik.ulm.de., de Pauw A; Department of Tumour Biology, Institut Curie, 26 rue d'Ulm 75248, Paris, cedex 05, France. antoine.depauw@curie.net., Lefol C; Department of Tumour Biology, Institut Curie, 26 rue d'Ulm 75248, Paris, cedex 05, France. cedrick.lefol@curie.net., Lasset C; UMR CNRS 5558, Laboratoire de Biométrie et Biologie Évolutive (LBBE), 'Biométrie et Biologie Évolutive', Université Claude Bernard Lyon 1, Bâtiment Grégor Mendel, 43 boulevard du 11 novembre 1918, 69622, Villeurbanne, cedex, France. christine.lasset@lyon.unicancer.fr.; Unité de Prévention et d'Épidémiologie Génétique, Centre Léon Bérard, 28 rue Laenned, 69008, Lyon, France. christine.lasset@lyon.unicancer.fr., Leroux D; Génétique Clinique, Centre Hospitalier Universitaire de Grenoble, CS 10217, 38043, Grenoble, cedex 9, France. dleroux@chu-grenoble.fr.; Institut Albert Bonniot - Inserm U823, Université Joseph Fourier, Rond-point de la Chantourne, 38706, La Tronche, France. dleroux@chu-grenoble.fr., Rouleau E; Laboratoire d'Oncogénétique, Hôpital René Huguenin, Institut Curie, 35 rue Dailly, 92210, Saint-Cloud, France. etienne.rouleau@curie.net., Damiola F; INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France. francesca.damiola@lyon.unicancer.fr., Dreyfus H; Génétique Clinique, Centre Hospitalier Universitaire de Grenoble, CS 10217, 38043, Grenoble, cedex 9, France. h.dreyfus@isc84.org.; Institut Albert Bonniot - Inserm U823, Université Joseph Fourier, Rond-point de la Chantourne, 38706, La Tronche, France. h.dreyfus@isc84.org., Barjhoux L; INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France. laure.barjhoux@lyon.unicancer.fr., Golmard L; Department of Tumour Biology, Institut Curie, 26 rue d'Ulm 75248, Paris, cedex 05, France. lisa.golmard@curie.net., Uhrhammer N; Département d'Oncogénétique, Centre Jean Perrin, Université de Clermont-Ferrand, 58 rue Montalembert, BP 392, 63011, Clermont-Ferrand, France. nancy.uhrammer@cjp.fr., Bonadona V; UMR CNRS 5558, Laboratoire de Biométrie et Biologie Évolutive (LBBE), 'Biométrie et Biologie Évolutive', Université Claude Bernard Lyon 1, Bâtiment Grégor Mendel, 43 boulevard du 11 novembre 1918, 69622, Villeurbanne, cedex, France. valerie.bonadona@lyon.unicancer.fr.; Unité de Prévention et d'Épidémiologie Génétique, Centre Léon Bérard, 28 rue Laenned, 69008, Lyon, France. valerie.bonadona@lyon.unicancer.fr., Sornin V; INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France. valerie.sornin@lyon.unicancer.fr., Bignon YJ; Département d'Oncogénétique, Centre Jean Perrin, Université de Clermont-Ferrand, 58 rue Montalembert, BP 392, 63011, Clermont-Ferrand, France. yves-jean.bignon@cjp.fr., Carter J; Gynaecological Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital and University of Sydney, Missenden Road, Camperdown, NSW, 2050, Australia. j.carter@sydney.edu.au., Van Le L; Gynecologic Oncology Group, Department of OB-GYN, University of North Carolina at Chapel Hill, 103B Physicians' Office Building, CB# 7572, Chapel Hill, NC, 27599-7572, USA. linda_van_le@med.unc.edu., Piedmonte M; Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263-0001, USA. mpiedmon@gogstats.org., DiSilvestro PA; Women & Infants Hospital, 1 Blackstone Place, Providence, RI, 02905, USA. pdisilvestro@wihri.org., de la Hoya M; Molecular Oncology Laboratory, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040, Madrid, Spain. mdhoya@hotmail.com., Caldes T; Molecular Oncology Laboratory, Health Research Institute of the San Carlos Clinical Hospital (IdISSC), 28040, Madrid, Spain. trinidad.caldes@salud.madrid.org., Nevanlinna H; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Biomedicum Helsinki, PO Box 700, 00029, Helsinki, Finland. heli.nevanlinna@hus.fi., Aittomäki K; Department of Clinical Genetics, Helsinki University Central Hospital, Biomedicum Helsinki 1, Haartmaninkatu 8, 00290, Helsinki, Finland. kristiina.aittomaki@hus.fi., Jager A; Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Center, PO Box 2040, 3000, CA, Rotterdam, the Netherlands. a.jager@erasmusmc.nl., van den Ouweland AM; Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center, Rotterdam, the Netherlands. a.vandenouweland@erasmusmc.nl., Kets CM; Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. marleen.kets@radboudumc.nl., Aalfs CM; Department of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands. c.m.aalfs@amc.uva.nl., van Leeuwen FE; Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands. f.v.leeuwen@nki.nl., Hogervorst FB; Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, the Netherlands. f.hogervorst@nki.nl., Meijers-Heijboer HE; Department of Clinical Genetics, VU University Medical Center Amsterdam, De Boelelaan 1118, 1081 HV, Amsterdam, the Netherlands. h.meijers@vumc.nl., Oosterwijk JC; Department of Genetics, University Medical Center, Groningen University, Groningen, the Netherlands. j.c.oosterwijk@umcg.nl., van Roozendaal KE; Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands. kees.vanroozendaal@mumc.nl., Rookus MA; Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands. m.rookus@nki.nl., Devilee P; Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, S4-P PO Box 9600, 2300, RC, Leiden, the Netherlands. p.devilee@lumc.nl.; Department of Pathology, Leiden University Medical Center, PO Box 9600, 2300 RC L1Q, Leiden, the Netherlands. p.devilee@lumc.nl., van der Luijt RB; Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands. r.b.vanderluijt@umcutrecht.nl., Olah E; Department of Molecular Genetics, National Institute of Oncology, Ráth György u 7-9, PO Box 1525 Budapest PF 21, 1122, Budapest, Hungary. e.olah@oncol.hu., Diez O; Oncogenetics Group, Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, Vall d'Hebron Research Institute (VHIR) and Universitat Autònoma de Barcelona, Passeig de la Vall d'Hebron 119, 08035, Barcelona, Spain. odiez@vhebron.net., Teulé A; Genetic Counseling Unit, Hereditary Cancer Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL)-Catalan Institute of Oncology, Hospital Duran i Reynals, 3a planta - Gran Via de l'Hospitalet, 199, 08908, Hospitalet de Llobregat, Barcelona, Spain. ateule@iconcologia.net., Lazaro C; Molecular Diagnostic Unit, Hereditary Cancer Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL)-Catalan Institute of Oncology, Hospital Duran i Reynals, 3a planta - Gran Via de l'Hospitalet, 199, 08908, Hospitalet de Llobregat, Barcelona, Spain. clazaro@iconcologia.net., Blanco I; Genetic Counseling Unit, Hereditary Cancer Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL)-Catalan Institute of Oncology, Hospital Duran i Reynals, 3a planta - Gran Via de l'Hospitalet, 199, 08908, Hospitalet de Llobregat, Barcelona, Spain. iblanco@iconcologia.net., Del Valle J; Molecular Diagnostic Unit, Hereditary Cancer Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL)-Catalan Institute of Oncology, Hospital Duran i Reynals, 3a planta - Gran Via de l'Hospitalet, 199, 08908, Hospitalet de Llobregat, Barcelona, Spain. jdelvalle@iconcologia.net., Jakubowska A; Department of Genetics and Pathomorphology, Faculty of Medicine and Dentistry, Pomeranian Medical University, al Powstancow Wlkp 72, 70-111, Szczecin, Poland. aniaj@pum.edu.pl., Sukiennicki G; Department of Genetics and Pathomorphology, Faculty of Medicine and Dentistry, Pomeranian Medical University, al Powstancow Wlkp 72, 70-111, Szczecin, Poland. starosta84@wp.pl., Gronwald J; Department of Genetics and Pathomorphology, Faculty of Medicine and Dentistry, Pomeranian Medical University, al Powstancow Wlkp 72, 70-111, Szczecin, Poland. jgron@pum.edu.pl., Lubinski J; Department of Genetics and Pathomorphology, Faculty of Medicine and Dentistry, Pomeranian Medical University, al Powstancow Wlkp 72, 70-111, Szczecin, Poland. lubinski@pum.edu.pl., Durda K; Department of Genetics and Pathomorphology, Faculty of Medicine and Dentistry, Pomeranian Medical University, al Powstancow Wlkp 72, 70-111, Szczecin, Poland. k.durda@onet.pl., Jaworska-Bieniek K; Department of Genetics and Pathomorphology, Faculty of Medicine and Dentistry, Pomeranian Medical University, al Powstancow Wlkp 72, 70-111, Szczecin, Poland. ka_jaworska@wp.pl., Agnarsson BA; Landspítali National University Hospital of Iceland and Faculty of Medicine, School of Health Sciences, University of Iceland School of Medicine, Sæmundargötu 2, 101, Reykjavik, Iceland. bjarniaa@lsh.is., Maugard C; Laboratoire de diagnostic génétique et Service d'Onco-hématologie, Les Hopitaux Universitaire de Strasbourg, Nouvel Hôpital Civil, 1 place de l'Hôpital, BP 426, 67091, Strasbourg, France. christinemaugard@gmail.com., Amadori A; Department of Surgical Sciences, Oncology and Gastroenterology, Padua University, Clinical Surgery II, via Giustiniani 2, 35124, Padua, Italy. albido@unipd.it.; Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto (IOV) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), via Gattamelata 64, 35128, Padua, Italy. albido@unipd.it., Montagna M; Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto (IOV) - Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), via Gattamelata 64, 35128, Padua, Italy. montagna@unipd.it., Teixeira MR; Department of Genetics, Portuguese Oncology Institute (IPO-PORTO), Edifício dos Laboratórios, piso 6, 4200-072, Porto, Portugal. manuel.teixeira@ipoporto.min-saude.pt.; Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal. manuel.teixeira@ipoporto.min-saude.pt., Spurdle AB; Department of Genetics and Computational Biology, QIMR Berghofer, Brisbane, Australia. amanda.spurdle@qimrberghofer.edu.au., Foulkes W; Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, 546 Pine Avenue West, Montreal, QC, J2W 1S6, Canada. william.foulkes@mcgill.ca., Olswold C; Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. olswold.curtis@mayo.edu., Lindor NM; Department of Health Sciences Research, Mayo Clinic, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA. lindor.noralane@mayo.edu., Pankratz VS; Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. pankratz.vernon@mayo.edu., Szabo CI; National Human Genome Research Institute, National Institutes of Health, Building 31, Room 4B09, 31 Center Drive, MSC 2152, 9000 Rockville Pike, Bethesda, MD, 20892-2152, USA. szaboc@mail.nih.gov., Lincoln A; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. lincolna@mskcc.org., Jacobs L; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. jacobsl@mskcc.org., Corines M; Clinical Genetics Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. corinesm@mskcc.org., Robson M; Clinical Genetics Research Laboratory, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. robsonm@mskcc.org., Vijai J; Clinical Genetics Research Laboratory, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. josephv@mskcc.org., Berger A; Department of Obstetrics and Gynecology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Universitätsklinik für Frauenheilkunde, AKH - Wien, Währinger Gürtel 18-20, 1090, Vienna, Austria. andreas.berger@meduniwien.ac.at., Fink-Retter A; Department of Obstetrics and Gynecology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Universitätsklinik für Frauenheilkunde, AKH - Wien, Währinger Gürtel 18-20, 1090, Vienna, Austria. anneliese.fink-retter@meduniwien.ac.at., Singer CF; Department of Obstetrics and Gynecology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Universitätsklinik für Frauenheilkunde, AKH - Wien, Währinger Gürtel 18-20, 1090, Vienna, Austria. christian.singer@meduniwien.ac.at., Rappaport C; Department of Obstetrics and Gynecology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Universitätsklinik für Frauenheilkunde, AKH - Wien, Währinger Gürtel 18-20, 1090, Vienna, Austria. christine.rappaport@akhwien.at., Kaulich DG; Department of Obstetrics and Gynecology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Universitätsklinik für Frauenheilkunde, AKH - Wien, Währinger Gürtel 18-20, 1090, Vienna, Austria. daphne.gschwantler-kaulich@meduniwien.ac.at., Pfeiler G; Department of Obstetrics and Gynecology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Universitätsklinik für Frauenheilkunde, AKH - Wien, Währinger Gürtel 18-20, 1090, Vienna, Austria. george.pfeiler@meduniwien.ac.at., Tea MK; Department of Obstetrics and Gynecology, Comprehensive Cancer Center Vienna, Medical University of Vienna, Universitätsklinik für Frauenheilkunde, AKH - Wien, Währinger Gürtel 18-20, 1090, Vienna, Austria. muy-kheng.tea@meduniwien.ac.at., Greene MH; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. greenem@mail.nih.gov., Mai PL; Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. maip@mail.nih.gov., Rennert G; Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Via Ripamonti 435, 20141, Milan, Italy. rennert@tx.technion.ac.il.; National Israeli Cancer Control Center and Department of Community Medicine and Epidemiology, Clalit Health Services Carmel Medical Center, 34361, Haifa, Israel. rennert@tx.technion.ac.il.; Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, 2 Horev Street, 34362, Haifa, Israel. rennert@tx.technion.ac.il., Imyanitov EN; NN Petrov Institute of Oncology, 68 Leningradskaya Street, Pesochny, 197758, St Petersburg, Russia. evgeny@imyanitov.spb.ru., Mulligan AM; Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building, 6th Floor, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. annamarie.mulligan@uhn.ca.; Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, 209 Victoria Street, Toronto, ON, M5B 1T8, Canada. annamarie.mulligan@uhn.ca., Glendon G; Ontario Cancer Genetics Network, Cancer Care Ontario, 620 University Avenue, Toronto, ON, M5G 2L7, Canada. gord.glendon@cancercare.on.ca.; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital Joseph and Wolf Lebovic Health Complex, 600 University Avenue, Toronto, ON, M5G 1X5, Canada. gord.glendon@cancercare.on.ca., Andrulis IL; Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building, 6th Floor, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. andrulis@lunenfeld.ca.; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital Joseph and Wolf Lebovic Health Complex, 600 University Avenue, Toronto, ON, M5G 1X5, Canada. andrulis@lunenfeld.ca.; Department of Molecular Genetics, University of Toronto, Medical Science Building, Room 4386, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. andrulis@lunenfeld.ca., Tchatchou S; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital Joseph and Wolf Lebovic Health Complex, 600 University Avenue, Toronto, ON, M5G 1X5, Canada. tchatchou@lunenfeld.ca., Toland AE; Department of Human Cancer Genetics, 1093 Biomedical Research Tower, 460 West 12th Avenue, Columbus, OH, 43210, USA. amanda.toland@osumc.edu.; Department of Internal Medicine, The Ohio State University Wexner Medical Center, North Doan Tower, 395 West 12th Avenue, Columbus, OH, 43210, USA. amanda.toland@osumc.edu.; Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, 1093 Biomedical Research Tower, 460 West 12th Avenue, Columbus, OH, 43210, USA. amanda.toland@osumc.edu.; The Ohio State University Comprehensive Cancer Center - Arthur G James Cancer Hospital and Richard J Solove Research Institute (OSUCCC - James), 460 West 10th Avenue, Columbus, OH, 43210, USA. amanda.toland@osumc.edu., Pedersen IS; Section of Molecular Diagnostics, Department of Biochemistry, Aalborg University Hospital, Hobrovej 18, 9000, Aalborg, Denmark. isp@rn.dk., Thomassen M; Department of Clinical Genetics, Odense University Hospital, Soenderboulevard 29, 5000, Odense C, Denmark. mads.thomassen@ouh.rsyd.dk., Kruse TA; Department of Clinical Genetics, Odense University Hospital, Soenderboulevard 29, 5000, Odense C, Denmark. torben.kruse@ouh.rsyd.dk., Jensen UB; Department of Clinical Genetics, Aarhus University Hospital, Brendstrupgårdsvej 21 C, 8200, Aarhus N, Denmark. uffejens@rm.dk., Caligo MA; Laboratorio di Genetica Oncologica, Divisione di Anatomia Patologica e di Diagnostica Molecolare ed Ultrastrutturale, Azienda Ospedaliero Universitaria Pisana - Ospedale S Chiara, via Roma 67, 56126, Pisa, Italy. adelaide.caligo@do.unipi.it., Friedman E; Sheba Laboratory of Molecular Genetics, The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Ramat Gan, 52621, Tel Aviv, Israel. eitan.friedman@sheba.health.gov.il., Zidan J; Institute of Oncology, Rivka Ziv Medical Center, Maimonides, 13100, Safed, Israel. jamal.zidan@ziv.health.gov.il., Laitman Y; Sheba Laboratory of Molecular Genetics, The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Ramat Gan, 52621, Tel Aviv, Israel. yael.laitman@sheba.health.gov.il., Lindblom A; Department of Cancer Genetics, Karolinska University Hospital, Solna L8:02, SE-171 76, Stockholm, Sweden. annika.lindblom@karolinska.se., Melin B; Oncology, Department of Radiation Sciences, Umeå University, SE-901 87, Umeå, Sweden. beatrice.melin@onkologi.umu.se., Arver B; Department of Oncology-Pathology, Karolinska University Hospital, K7, Ärftlighetsmottagningen, Radiumhemmet, 171 76, Stockholm, Sweden. brita.wasteson-arver@karolinska.se., Loman N; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University Hospital, Barngatan 2B, SE-221 85, Lund, Sweden. niklas.loman@med.lu.se., Rosenquist R; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85, Uppsala, Sweden. richard.rosenquist@igp.uu.se., Olopade OI; Center for Clinical Cancer Genetics and Global Health, The University of Chicago, 5841 South Maryland Avenue, Chicago, IL, 60637, USA. folopade@medicine.bsd.uchicago.edu., Nussbaum RL; Department of Medicine and Genetics, University of California, San Francisco, CA, USA. nussbaumr@humgen.ucsf.edu., Ramus SJ; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Norris Comprehensive Cancer Center, NOR-4435, Los Angeles, CA, 90089-9175, USA. sramus@usc.edu., Nathanson KL; Department of Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Suite 750, Philadelphia, PA, 19104-3309, USA. knathans@exchange.upenn.edu., Domchek SM; Department of Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Suite 750, Philadelphia, PA, 19104-3309, USA. susan.domchek@uphs.upenn.edu., Rebbeck TR; Department of Epidemiology and Biostatistics, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Suite 750, Philadelphia, PA, 19104-3309, USA. rebbeck@exchange.upenn.edu., Arun BK; Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 1354, PO Box 301439, Houston, TX, 77230-1439, USA. barun@mdanderson.org., Mitchell G; Sir Peter MacCallum Department of Oncology, Familial Cancer Centre, Peter MacCallum Cancer Centre, level 3, 10 St Andrews Place, East Melbourne, VIC, 3002, Australia. gillian.mitchell@petermac.org.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Level 5, 161 Barry Street, Parkville, 3010, VIC, Australia. gillian.mitchell@petermac.org., Karlan BY; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA. beth.karlan@cshs.org., Lester J; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA. jenny.lester@cshs.org., Orsulic S; Women's Cancer Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, 90048, USA. sandra.orsulic@cshs.org., Stoppa-Lyonnet D; Department of Tumour Biology, Institut Curie, 26 rue d'Ulm 75248, Paris, cedex 05, France. dominique.stoppa-lyonnet@curie.net.; Service de génétique oncologique, Institut Curie, Inserm U830, 26 rue d'Ulm, 75248, Paris, France. dominique.stoppa-lyonnet@curie.net.; Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, 15 rue de l'école de médecine, 75006, Paris, France. dominique.stoppa-lyonnet@curie.net., Thomas G; Génétique médicale, Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, 8 avenue Rockefeller, 69373, Lyon, Cedex 08, France.; Institut National du Cancer (INCa), La Fondation Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laënnec, 69008, Lyon, Cedex 08, France., Simard J; Centre de recherche du Centre hospitalier universitaire de Québec, Laval University, Charlesbourg, PQ, Canada. jacques.simard@crchul.ulaval.ca., Couch FJ; Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. couch.fergus@mayo.edu.; Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. couch.fergus@mayo.edu., Offit K; Clinical Genetics Research Laboratory, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. offitk@mskcc.org., Easton DF; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. douglas@srl.cam.ac.uk., Chenevix-Trench G; Department of Genetics and Computational Biology, QIMR Berghofer, Brisbane, Australia. georgia.trench@qimrberghofer.edu.au., Antoniou AC; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. antonis@srl.cam.ac.uk., Mazoyer S; INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France. sylvie.mazoyer@lyon.unicancer.fr.; Université de Lyon, 69000, Lyon, France. sylvie.mazoyer@lyon.unicancer.fr.; Université Lyon 1, 69100, Villeurbanne, France. sylvie.mazoyer@lyon.unicancer.fr., Phelan CM; Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA. catherine.phelan@moffitt.org., Sinilnikova OM; INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France.; Université de Lyon, 69000, Lyon, France.; Université Lyon 1, 69100, Villeurbanne, France.; Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon - Centre Léon Bérard, 69373, Lyon, Cedex 08, France., Cox DG; INSERM U1052, CNRS UMR5286, Université Lyon 1, Centre de Recherche en Cancérologie de Lyon, Lyon, France. david.cox@lyon.unicancer.fr.; Université de Lyon, 69000, Lyon, France. david.cox@lyon.unicancer.fr.; Université Lyon 1, 69100, Villeurbanne, France. david.cox@lyon.unicancer.fr.
Jazyk:	angličtina
Zdroj:	Breast cancer research : BCR [Breast Cancer Res] 2015 Apr 25; Vol. 17, pp. 61. Date of Electronic Publication: 2015 Apr 25.
DOI:	10.1186/s13058-015-0567-2
Abstrakt:	Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink