Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers.

Creators: Antoniou, Antonis C; Kartsonaki, Christiana; Sinilnikova, Olga M; Soucy, Penny; Mcguffog, Lesley; Healey, Sue; Lee, Andrew; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Cattaneo, Elisa; Barile, Monica; Pensotti, Valeria; Pasini, Barbara; Dolcetti, Riccardo; Giannini, Giuseppe; Putignano, Anna Laura; Varesco, Liliana; Radice, Paolo; Mai, Phuong L; Greene, Mark H; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A; Birk Jensen, Uffe; Crüger, Dorthe G; Caligo, Maria A; Laitman, Yael; Milgrom, Roni; Kaufman, Bella; Paluch-Shimon, Shani; Friedman, Eitan; Loman, Niklas; Harbst, Katja; Lindblom, Annika; Arver, Brita; Ehrencrona, Hans; Melin, Beatrice; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy; Jakubowska, Ania; Lubinski, Jan; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Gorski, Bohdan; Osorio, Ana; Ramón y Cajal, Teresa; Fostira, Florentia; Andrés, Raquel; Benitez, Javier; Hamann, Ute; Hogervorst, Frans B; Rookus, Matti A; Hooning, Maartje J; Nelen, Marcel R; van Der Luijt, Rob B; van Os, Theo a M; van Asperen, Christi J; Devilee, Peter; Meijers-Heijboer, Hanne E J; Gómez Garcia, Encarna B; Peock, Susan; Cook, Margaret; Frost, Debra; Platte, Radka; Leyland, Jean; Evans, D Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Ong, Kai-Ren; Cook, Jackie; Douglas, Fiona; Paterson, Joan; Kennedy, M John; Miedzybrodzka, Zosia; Godwin, Andrew; Stoppa-Lyonnet, Dominique; Buecher, Bruno; Belotti, Muriel; Tirapo, Carole; Mazoyer, Sylvie; Barjhoux, Laure; Lasset, Christine; Leroux, Dominique; Faivre, Laurence; Bronner, Myriam; Prieur, Fabienne; Nogues, Catherine; Rouleau, Etienne; Pujol, Pascal; Coupier, Isabelle; Frénay, Marc; Hopper, John L; Daly, Mary B; Terry, Mary B; John, Esther M; Buys, Saundra S; Yassin, Yosuf; Miron, Alexander; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Dressler, Anne Catharina; Hansen, Thomas V O; Jønson, Lars; Ejlertsen, Bent; Barkardottir, Rosa Bjork; Kirchhoff, Tomas; Offit, Kenneth; Piedmonte, Marion; Rodriguez, Gustavo; Small, Laurie; Boggess, John; Blank, Stephanie; Basil, Jack; Azodi, Masoud; Toland, Amanda Ewart; Montagna, Marco; Tognazzo, Silvia; Agata, Simona; Imyanitov, Evgeny; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Pharoah, Paul D P; Sucheston, Lara; Karlan, Beth y; Walsh, Christine S; Olah, Edith; Bozsik, Aniko; Teo, Soo-Hwang; Seldon, Joyce L; Beattie, Mary S; van Rensburg, Elizabeth J; Sluiter, Michelle D; Diez, Orland; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ruehl, Ina; Varon-Mateeva, Raymonda; Kast, Karin; Deissler, Helmut; Niederacher, Dieter; Arnold, Norbert; Gadzicki, Dorothea; Schönbuchner, Ines; Caldes, Trinidad; de La Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Dumont, Martine; Chiquette, Jocelyne; Tischkowitz, Marc; Chen, Xiaoqing; Beesley, Jonathan; Spurdle, Amanda B; Neuhausen, Susan L; Chun Ding, Yuan; Fredericksen, Zachary; Wang, Xianshu; Pankratz, Vernon S; Couch, Fergus; Simard, Jacques; Easton, Douglas F; Chenevix-Trench, Georgia; Renseigné, Non

Others:: Centre for Cancer Genetic Epidemiology ; University of Cambridge [UK] (CAM); Cancer Genomics Laboratory ; Centre Hospitalier Universitaire de Québec; Queensland Institute of Medical Research; Unit of Molecular Bases of Genetic Risk and Genetic Testing ; Fondazione IRCCS Istituto Nazionale Tumouri (INT)-Fondazione Istituto FIRC di Oncologia Molecolare; Unit of Medical Genetics ; Fondazione IRCCS Istituto Nazionale Tumouri (INT); Unit of Medical Genetics ; Fondazione IRCCS Istituto Nazionale Tumouri (INT); Division of Cancer Prevention and Genetics ; Istituto Europeo di Oncologia (IEO); Consortium for Genomics Technology (Cogentech) ; Consortium for Genomics Technology (Cogentech); Department of Genetics, Biology and Biochemistry ; Università degli studi di Torino = University of Turin (UNITO); Cancer Bioimmunotherapy Unit ; IRCCS-Centro di Riferimento Oncologico; Department of Experimental Medicine ; Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome] (UNIROMA); Medical Genetics Unit, Department of Clinical Physiopathology ; Università degli Studi di Firenze = University of Florence (UniFI); Unit of Hereditary Cancers ; Istituto Nazionale per la Ricerca sul Cancro; Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics ; National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH) ; National Institutes of Health [Bethesda] (NIH); Ontario Cancer Genetics Network ; Cancer Care Ontario; Departments of Molecular Genetics and Laboratory Medicine and Pathobiology ; University of Toronto-Cancer Care Ontario; Samuel Lunenfeld Research Institute ; Mount Sinai Hospital [Toronto, Canada] (MSH); Department of Clinical Genetics ; Odense University Hospital; Department of Clinical Genetics [Copenhagen] ; Rigshospitalet [Copenhagen] ; Copenhagen University Hospital-Copenhagen University Hospital; The Susanne Levy Gertner Oncogenetics Unit ; Institute of Human Genetics; Sackler Faculty of Medicine ; Tel Aviv University [Tel Aviv]; Department of Oncology ; Lund University Hospital; Department of Clinical Genetics ; Karolinska University Hospital [Stockholm]; Department of Oncology ; Karolinska University Hospital [Stockholm]; Department of Genetics and Pathology ; Uppsala University; Department of Radiation Sciences and Oncology ; Umeå University; Depts of Medicine and Biostatistics and Epidemology ; Abramson Family Cancer Research Institute-Perelman School of Medicine ; University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]; Center for Clinical Epidemiology and Biostatistics ; Abramson Cancer Center-Perelman School of Medicine ; University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]; Department of Genetics and Pathology ; International Hereditary Cancer Centre-Pomeranian Medical University [Szczecin] (PUM); Department of Genetics and Pathology, International Hereditary Cancer Center ; Pomeranian Medical University [Szczecin] (PUM); Department of Genetics and Pathology ; International Hereditary Cancer Center, Pomeranian Medical University; Human Genetics Group ; Spanish National Cancer Research Centre; Biomedical Research Centre Network for Rare Diseases ; CIBER de Enfermedades Raras (CIBERER); Department of Medical Oncology ; Hospital de la Santa Creu i Sant Pau; Medical Oncology Division ; Hospital Clínico de Zaragoza; Molecular Genetics of Breast Cancer ; German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ); Department of Genetic Epidemiology ; Leiden University Medical Center (LUMC); Genetic Medicine ; Manchester Academic Health Sciences Centre-Central Manchester University Hospitals; Oncogenetics Team ; The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; Clinical Genetics ; Guy's and St. Thomas' NHS Foundation Trust; Yorkshire Regional Genetics Service ; Yorkshire Regional Genetics Service; Ferguson-Smith Centre for Clinical Genetics ; Yorkhill Hospitals; Wessex Clinical Genetics Service ; Princess Anne Hospital; West Midlands Regional Genetics Service ; Birmingham Women's and Children's NHS Foundation Trust; Sheffield Clinical Genetics Service ; Sheffield Children's NHS Foundation Trust; Institute of Human Genetics ; Newcastle Upon Tyne Hospitals NHS Foundation Trust; Department of Clinical Genetics ; Addenbrookes Hospital; Department of Pathology and Laboratory Medicine ; University of Kansas Medical Center [Kansas City, KS, USA]; Service de Génétique Oncologique ; Institut Curie [Paris]; Unité de génétique et biologie des cancers (U830) ; Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM); génétique ; Institut Curie [Paris]; Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL) ; Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents ; Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL); Biostatistiques santé ; Département biostatistiques et modélisation pour la santé et l'environnement [LBBE] ; Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS); Equipe de prévention et épidémiologie génétique ; Centre Léon Bérard [Lyon]; Service d'onco-hématologie et génétique ; CHU Grenoble; Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon) ; Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon); Service de Génétique Clinique Chromosomique et Moléculaire ; CHU Saint-Etienne; Santé Publique ; Institut Curie [Paris]-Hôpital René HUGUENIN (Saint-Cloud); Laboratoire d'Oncogénétique ; CRLCC René Huguenin; Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1) ; Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM); Service de génétique médicale [Montpellier] ; Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve; Unité d'Oncogénétique ; CRLCC Val d'Aurelle - Paul Lamarque; Consultation d'oncogénétique ; Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL) ; UNICANCER-Université Côte d'Azur (UCA)-UNICANCER-Université Côte d'Azur (UCA); Department of Cancer Biology ; Dana-Farber Cancer Institute [Boston]; Department of Surgery ; Harvard Medical School [Boston] (HMS); Department of Dermatology ; University of Utah School of Medicine [Salt Lake City]; Dept of OB/GYN and Comprehensive Cancer Center ; Medizinische Universität Wien = Medical University of Vienna; Division of Special Gynecology ; Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN; Department of Clinical Biochemistry [Rigshospitalet] ; Rigshospitalet [Copenhagen] ; Copenhagen University Hospital-Copenhagen University Hospital; Department of Oncology ; Copenhagen University Hospital-Rigshospitalet [Copenhagen] ; Copenhagen University Hospital; Department of Pathology ; Landspitali-University Hospital; Department of Environmental Medicine ; New York University School of Medicine ; NYU System (NYU)-NYU System (NYU)-NYU Cancer Institute; Clinical Genetics Service ; Memorial Sloane Kettering Cancer Center [New York]; Statistical and Data Center ; Roswell Park Cancer Institute [Buffalo]; Immunology and Molecular Oncology Unit ; Istituto Oncologico Veneto IOV - IRCCS; Immunology and Molecular Oncology Unit ; Istituto Oncologico Veneto IOV - IRCCS; Laboratory of Molecular Oncology ; N.N. Petrov Institute of Oncology; Department of Molecular and Regenerative Medicine, Hematology, Oncology and Transfusion Medicine Center ; Vilnius University Hospital Santariskiu Clinics; State Research Institute Innovative Medicine Center ; State Research Institute Innovative Medicine Center; Molecular Diagnostic Unit ; IDIBELL-Catalan Institute of Oncology; Genetic Counselling Unit ; IDIBELL-Catalan Institute of Oncology; Department of Molecular Genetics ; National Institute of Oncology; Cancer Research Initiatives Foundation ; Sime Darby Medical Centre-Malaysia and University Malaya Cancer Research Institute-University Malaya Medical Centre; Oncogenetics Laboratory ; Vall d'Hebron Institute of Oncology (VHIO); Department of Gynaecology and Obstetrics ; University Hospital of Cologne [Cologne]-Centre of Familial Breast and Ovarian Cancer-Centre for Integrated Oncology (CIO); Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] (IMISE) ; Universität Leipzig [Leipzig]; Department of Gynaecology and Obstetrics ; Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM); Department of Gynaecology and Obstetrics ; Ludwig-Maximillians University; Institute of Human Genetics ; Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]; Department of Gynaecology and Obstetrics ; University Hospital Carl Gustav Carus; Department of Gynaecology and Obstetrics ; Universitätsklinikum Ulm - University Hospital of Ulm; Department of Gynaecology and Obstetrics ; University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]; Department of Gynaecology and Obstetrics ; University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU); Institute of Cell and Molecular Pathology ; Hannover Medical School [Hannover] (MHH); Institute of Human Genetics ; Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU); Molecular Oncology Laboratory ; Hospital Clínico San Carlos; Department of Obstetrics and Gynecology ; Helsinki University Central Hospital; Department of Clinical Genetics ; Helsinki University Central Hospital; Department of Genetics ; Portuguese Oncology Institute; Department of Medical Genetics ; Mayo Clinic; Department of Laboratory Medicine and Pathology ; Mayo Clinic; Department of Laboratory Medicine and Pathology ; Mayo Clinic; Cancer Research U.K. Genetic Epidemiology Unit ; Strangeways Research Laboratory; Genetic Epidemiology Unit, Department of Public Health and Primary Care ; University of Cambridge [UK] (CAM)

Description

Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.

Abstract

International audience

Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers.

Description

Abstract

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