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51. Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers

Author: Cox, D. G., Simard, J., Sinnett, D., Hamdi, Y., Soucy, P., Ouimet, M., Barjhoux, L., Verny-Pierre, C., McGuffog, L., Healey, S., Szabo, C., Greene, M. H., Mai, P. L., Andrulis, I. L., Thomassen, M., Gerdes, A.-M., Caligo, M. A., Friedman, E., Laitman, Y., Kaufman, B., Paluch, S. S., Borg, A., Karlsson, P., Stenmark Askmalm, M., Barbany Bustinza, G., Nathanson, K. L., Domchek, S. M., Rebbeck, T. R., Benitez, J., Hamann, U., Rookus, M. A., van den Ouweland, A. M. W., Ausems, M. G. E. M., Aalfs, C. M., van Asperen, C. J., Devilee, P., Gille, H. J. J. P., Peock, S., Frost, D., Evans, D. G., Eeles, R., Izatt, L., Adlard, J., Paterson, J., Eason, J., Godwin, A. K., Remon, M.-A., Moncoutier, V., Gauthier-Villars, M., Lasset, C., Giraud, S., Hardouin, A., Berthet, P., Sobol, H., Eisinger, F., Bressac de Paillerets, B., Caron, O., Delnatte, C., Goldgar, D., Miron, A., Ozcelik, H., Buys, S., Southey, M. C., Terry, M. B., Singer, C. F., Dressler, A.-C., Tea, M.-K., Hansen, T. V. O., Johannsson, O., Piedmonte, M., Rodriguez, G. C., Basil, J. B., Blank, S., Toland, A. E., Montagna, M., Isaacs, C., Blanco, I., Gayther, S. A., Moysich, K. B., Schmutzler, R. K., Wappenschmidt, B., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Niederacher, D., Sutter, C., Gadzicki, D., Fiebig, B., Caldes, T., Laframboise, R., Nevanlinna, H., Chen, X., Beesley, J., Spurdle, A. B., Neuhausen, S. L., Ding, Y. C., Couch, F. J., Wang, X., Peterlongo, P., Manoukian, S., Bernard, L., Radice, P., Easton, D. F., Chenevix-Trench, G., Antoniou, A. C., Stoppa-Lyonnet, D., Mazoyer, S., Sinilnikova, O. M., Dumont, M., Greene, M., Glendon, G., Selander, T., Weerasooriya, N., Nordling, M., Bergman, A., Einbeigi, Z., Stenmark-Askmalm, M., Liedgren, S., Loman, N., Olsson, H., Kristoffersson, U., Soller, M., Jernstrom, H., Harbst, K., Henriksson, K., Lindblom, A., Arver, B., von Wachenfeldt, A., Liljegren, A., Barbany-Bustinza, G., Rantala, J., Melin, B., Gronberg, H., Stattin, E.-L., Emanuelsson, M., Ehrencrona, H., Torres, D., Rashid, M. U., Seidel-Renkert, A., Hogervorst, F. B. L., Verhoef, S., Verheus, M., van't Veer, L. J., van Leeuwen, F. E., Collee, M., Jager, A., Hooning, M. J., Tilanus-Linthorst, M. M. A., Seynaeve, C., Wijnen, J. T., Vreeswijk, M. P., Tollenaar, R. A., Ligtenberg, M. J., Hoogerbrugge, N., Ausems, M. G., van der Luijt, R. B., van Os, T. A., Gille, J. J. P., Waisfisz, Q., Meijers-Heijboer, H. E. J., Gomez-Garcia, E. B., van Roozendaal, C. E., Blok, M. J., Caanen, B., Oosterwijk, J. C., van der Hout, A. H., Mourits, M. J., Vasen, H. F., Cook, M., Platte, R., Miedzybrodzka, Z., Gregory, H., Morrison, P., Jeffers, L., Cole, T., Ong, K.-r., Hoffman, J., Donaldson, A., James, M., Downing, S., Taylor, A., Murray, A., Rogers, M. T., McCann, E., Kennedy, M. J., Barton, D., Porteous, M., Drummond, S., Brewer, C., Kivuva, E., Searle, A., Goodman, S., Hill, K., Davidson, R., Murday, V., Bradshaw, N., Snadden, L., Longmuir, M., Watt, C., Gibson, S., Haque, E., Tobias, E., Duncan, A., Jacobs, C., Langman, C., Whaite, A., Dorkins, H., Barwell, J., Chu, C., Miller, J., Ellis, I., Houghton, C., Lalloo, F., Taylor, J., Side, L., Male, A., Berlin, C., Collier, R., Douglas, F., Claber, O., Jobson, I., Walker, L., McLeod, D., Halliday, D., Durell, S., Stayner, B., Shanley, S., Rahman, N., Houlston, R., Bancroft, E., D'Mello, L., Page, E., Ardern-Jones, A., Kohut, K., Wiggins, J., Castro, E., Mitra, A., Robertson, L., Cook, J., Quarrell, O., Bardsley, C., Hodgson, S., Goff, S., Brice, G., Winchester, L., Eddy, C., Tripathi, V., Attard, V., Eccles, D., Lucassen, A., Crawford, G., McBride, D., Smalley, S., Sinilnikova, O., Leone, M., Buecher, B., Houdayer, C., Belotti, M., Tirapo, C., de Pauw, A., Bressac-de-Paillerets, B., Remenieras, A., Byrde, V., Lenoir, G., Bignon, Y.-J., Uhrhammer, N., Bonadona, V., Bourdon, V., Noguchi, T., Coulet, F., Colas, C., Soubrier, F., Coupier, I., Pujol, P., Peyrat, J.-P., Fournier, J., Revillion, F., Vennin, P., Adenis, C., Rouleau, E., Lidereau, R., Demange, L., Nogues, C., Muller, D., Fricker, J.-P., Longy, M., Sevenet, N., Toulas, C., Guimbaud, R., Gladieff, L., Feillel, V., Leroux, D., Dreyfus, H., Rebischung, C., Coron, F., Faivre, L., Prieur, F., Lebrun, M., Ferrer, S. F., Frenay, M., Venat-Bouvet, L., Mortemousque, I., Lynch, H. T., Snyder, C. L., Ejlertsen, B., Andersen, M. K., Kjaergaard, S., Senter, L., Sweet, K., O'Connor, M., Craven, C., Pharoah, P., Ramus, S., Pye, C., Harrington, P., Wozniak, E., Varon-Mateeva, R., Kast, K., Preisler-Adams, S., Deissler, H., Schonbuchner, I., Heinritz, W., Schafer, D., Aittomaki, K., Blomqvist, C., Heikkinen, T., Erkkila, R. N. I., Thorne, H., Niedermayr, E., de la Hoya, M., Perez-Segura, P., 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), Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Québec, Centre de recherche du CHU Sainte-Justine [Montreal], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Department of Pediatrics, CHU Sainte Justine [Montréal], Centre for Cancer Genetic Epidemiology, University of Cambridge [UK] (CAM), Queensland Institute of Medical Research, University of Delaware [Newark], 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), Department of Clinical Genetics, Odense University Hospital, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], The Susanne Levy Gertner Oncogenetics Unit, Institute of Human Genetics, Department of Oncology, Clinical Sciences, Lund University [Lund]-Skåne University Hospital, Department of Oncology, Sahlgrenska University Hospital [Gothenburg], Depts of Medicine and Biostatistics and Epidemology, Abramson Family Cancer Research Institute-Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Human Genetics Group, Spanish National Cancer Research Centre, Biomedical Research Centre Network for Rare Diseases, CIBER de Enfermedades Raras (CIBERER), 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, Addenbrookes Hospital, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust, génétique, Institut Curie [Paris], Service de Génétique Oncologique, 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 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], Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Consultation d'Oncogénétique, Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Service d'Oncologie Génétique, de Prévention et Dépistage, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique oncologique (GO - UMR 8125), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Centre René Gauducheau, CRLCC René Gauducheau, Department of Dermatology, University of Utah School of Medicine [Salt Lake City], 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 Internal Medicine, Huntsman Cancer Institute, Division of Special Gynecology, Medizinische Universität Wien = Medical University of Vienna-Department of OB/GYN, Dept of OB/GYN and Comprehensive Cancer Center, Medizinische Universität Wien = Medical University of Vienna, Faculty of Medicine, University of Iceland [Reykjavik], Statistical and Data Center, Roswell Park Cancer Institute [Buffalo], Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, Lombardi Comprehensive Cancer Center, Georgetown University, Genetic Counselling Unit, IDIBELL-Catalan Institute of Oncology, 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], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Ludwig-Maximilians-Universität München (LMU), University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel (CAU), University Hospital Düsseldorf-Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Heidelberg University Hospital [Heidelberg], Institute of Cell and Molecular Pathology, Hannover Medical School [Hannover] (MHH), Universität Regensburg (UR), Molecular Oncology Laboratory, Hospital Clínico San Carlos, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Department of Laboratory Medicine and Pathology, Mayo Clinic, 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), Department of Experimental Oncology, Istituto Europeo di Oncologia-Consortium for Genomics Technology (Cogentech), Cancer Research U.K. Genetic Epidemiology Unit, Strangeways Research Laboratory, Genetic Epidemiology Unit, Department of Public Health and Primary Care, 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), Equipe 6, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Research Centre, CHU Ste Justine, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Génétique moléculaire, signalisation et cancer (GMSC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Human Genetics, Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Tel Aviv University (TAU), University of Pennsylvania-University of Pennsylvania, Universiteit Leiden-Universiteit Leiden, Nottingham University Hospitals NHS Trust (NUH), Roswell Park Cancer Institute [Buffalo] (RPCI), Georgetown University [Washington] (GU), Universität Leipzig, Centre de Recherche en Cancérologie de Lyon ( 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 ) -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 ), 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 ) -Hospices Civils de Lyon ( HCL ), Génétique moléculaire, signalisation et cancer ( GMSC ), Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University of Cambridge [UK] ( CAM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Rigshospitalet [Copenhagen]-University of Copenhagen ( KU ), Sahlgrenska University Hospital, Abramson Family Cancer Research Institute-University of Pennsylvania School of Medicine, Deutsches Krebsforschungszentrum ( DKFZ ), INSTITUT CURIE, Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Centre François Baclesse, Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale ( SESSTIM - U912 INSERM - AMU - IRD ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ), Génétique oncologique ( GO - UMR 8125 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Centre National de la Recherche Scientifique ( CNRS ), Mount Sinai Hospital ( MSH ), Medical University of Vienna-Department of OB/GYN, Medical University of Vienna, Institute for Medical Informatics, Statistics and Epidemiology [Leipzig] ( IMISE ), University of Leipzig, Technical University of Munich ( TUM ), Ludwig-Maximilians-Universität München, University Hospital of Schleswig-Holstein-Christian-Albrechts-Universität zu Kiel ( CAU ), University Hospital Düsseldorf-Heinrich-Heine-Universität Düsseldorf [Düsseldorf], Hannover Medical School [Hannover] ( MHH ), University Regensburg, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Human genetics, and CCA - Oncogenesis
Subjects: endocrine system diseases, Electrophoretic Mobility Shift Assay, MESH : Breast Neoplasms, medicine.disease_cause, Linkage Disequilibrium, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Genes, Reporter, Risk Factors, MESH: Risk Factors, Genotype, MESH : Female, Luciferases, skin and connective tissue diseases, Genetics (clinical), MESH: Genetic Association Studies, MESH: Heterozygote, Genetics, 0303 health sciences, MESH : Linkage Disequilibrium, BRCA1 Protein, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Association Studies Articles, MESH: Genetic Predisposition to Disease, General Medicine, MESH : Genes, Reporter, MESH : Risk Factors, 3. Good health, MESH: Linkage Disequilibrium, 030220 oncology & carcinogenesis, MESH : Electrophoretic Mobility Shift Assay, Female, Breast disease, MESH : Mutation, MESH : Heterozygote, Heterozygote, MESH: Mutation, Single-nucleotide polymorphism, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, medicine, Humans, MESH : BRCA1 Protein, MESH : HeLa Cells, Genetic Predisposition to Disease, ddc:610, Allele, Molecular Biology, MESH : Haplotypes, Alleles, Genetic Association Studies, 030304 developmental biology, MESH: BRCA1 Protein, MESH : Luciferases, MESH: Humans, Hereditary cancer and cancer-related syndromes [ONCOL 1], MESH: Alleles, Haplotype, MESH : Humans, MESH: Genes, Reporter, Cancer, MESH : Genetic Association Studies, MESH: Haplotypes, medicine.disease, Haplotypes, Mutation, MESH: Electrophoretic Mobility Shift Assay, MESH: HeLa Cells, Cancer research, MESH : Genetic Predisposition to Disease, MESH: Luciferases, Carcinogenesis, MESH : Alleles, MESH: Female, MESH: Breast Neoplasms, HeLa Cells
Abstract: Item does not contain fulltext Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription.
Published: 2011
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52. Familial hematological malignancies: ASXL1 gene investigation

Author: Hamadou, W. S., primary, Abed, R. E., additional, Besbes, S., additional, Bourdon, V., additional, Fabre, A., additional, Youssef, Y. B., additional, Laatiri, M. A., additional, Eisinger, F., additional, Mari, V., additional, Gesta, P., additional, Dreyfus, H., additional, Bonadona, V., additional, Dugast, C., additional, Zattara, H., additional, Faivre, L., additional, Jemni, S. Y., additional, Noguchi, T., additional, Khélif, A., additional, Sobol, H., additional, and Soua, Z., additional
Published: 2015
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53. Common Breast Cancer Susceptibility Alleles and the Risk of Breast Cancer for BRCA1 and BRCA2 Mutation Carriers: Implications for Risk Prediction

Author: Antoniou, A.C., Beesley, J., McGuffog, L., Sinilnikova, O.M., Healey, S., Neuhausen, S.L., Ding, Y.C., Rebbeck, T.R., Weitzel, J.N., Lynch, H.T., Isaacs, C., Ganz, P.A., Tomlinson, G., Olopade, O.I., Couch, F.J., Wang, X.S., Lindor, N.M., Pankratz, V.S., Radice, P., Manoukian, S., Peissel, B., Zaffaroni, D., Barile, M., Viel, A., Allavena, A., Dall'Olio, V., Peterlongo, P., Szabo, C.I., Zikan, M., Claes, K., Poppe, B., Foretova, L., Mai, P.L., Greene, M.H., Rennert, G., Lejbkowicz, F., Glendon, G., Ozcelik, H., Andrulis, I.L., Thomassen, M., Gerdes, A.M., Sunde, L., Cruger, D., Jensen, U.B., Caligo, M., Friedman, E., Kaufman, B., Laitman, Y., Milgrom, R., Dubrovsky, M., Cohen, S., Borg, A., Jernstrom, H., Lindblom, A., Rantala, J., Stenmark-Askmalm, M., Melin, B., Nathanson, K., Domchek, S., Jakubowska, A., Lubinski, J., Huzarski, T., Osorio, A., Lasa, A., Duran, M., Tejada, M.I., Godino, J., Benitez, J., Hamann, U., Kriege, M., Hoogerbrugge, N., Luijt, R.B. van der, Asperen, C.J. van, Devilee, P., Meijers-Heijboer, E.J., Blok, M.J., Aalfs, C.M., Hogervorst, F., Rookus, M., Cook, M., Oliver, C., Frost, D., Conroy, D., Evans, D.G., Lalloo, F., Pichert, G., Davidson, R., Cole, T., Cook, J., Paterson, J., Hodgson, S., Morrison, P.J., Porteous, M.E., Walker, L., Kennedy, M.J., Dorkins, H., Peock, S., Godwin, A.K., Stoppa-Lyonnet, D., Pauw, A. de, Mazoyer, S., Bonadona, V., Lasset, C., Dreyfus, H., Leroux, D., Hardouin, A., Berthet, P., Faivre, L., Loustalot, C., Noguchi, T., Sobol, H., Rouleau, E., Nogues, C., Frenay, M., Venat-Bouvet, L., Hopper, J.L., Daly, M.B., Terry, M.B., John, E.M., Buys, S.S., Yassin, Y., Miron, A., Goldgar, D., Singer, C.F., Dressler, A.C., Gschwantler-Kaulich, D., Pfeiler, G., Hansen, T.V.O., Jnson, L., Agnarsson, B.A., Kirchhoff, T., Offit, K., Devlin, V., Dutra-Clarke, A., Piedmonte, M., Rodriguez, G.C., Wakeley, K., Boggess, J.F., Basil, J., Schwartz, P.E., Blank, S.V., Toland, A.E., Montagna, M., Casella, C., Imyanitov, E., Tihomirova, L., Blanco, I., Lazaro, C., Ramus, S.J., Sucheston, L., Karlan, B.Y., 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., Schonbuchner, I., Caldes, T., Hoya, M. de la, Aittomaki, K., Nevanlinna, H., Simard, J., Spurdle, A.B., Holland, H., Chen, X.Q., Platte, R., Chenevix-Trench, G., Easton, D.F., Ontario Canc Genetics Network, SWE-BRCA, HEBON, EMBRACE, GEMO, Breast Canc Family Registry, kConFab, CIMBA, MUMC+: DA KG Lab Centraal Lab (9), Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Human genetics, CCA - Oncogenesis, Human Genetics, Pathology, Clinical Genetics, Pediatric Surgery, Medical Oncology, and Internal Medicine
Subjects: Oncology, Cancer Research, endocrine system diseases, Vesicular Transport Proteins, Gene mutation, 0302 clinical medicine, Risk Factors, Genotype, skin and connective tissue diseases, Aged, 80 and over, 0303 health sciences, BRCA1 Protein, High Mobility Group Proteins, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Female, Breast disease, Receptors, Progesterone, Adult, Heterozygote, medicine.medical_specialty, Breast Neoplasms, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Risk Assessment, Article, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Alleles, Aged, 030304 developmental biology, BRCA2 Protein, Hereditary cancer and cancer-related syndromes [ONCOL 1], Sodium-Bicarbonate Symporters, Haplotype, Cancer, genome-wide association estrogen-receptor loci variants, medicine.disease, Survival Analysis, TOX3, Mutation, Trans-Activators, Cancer research, Apoptosis Regulatory Proteins
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.
Published: 2010
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54. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Author: Kuchenbaecker, K.B. (Karoline), Neuhausen, S.L. (Susan), Robson, M. (Mark), Barrowdale, D. (Daniel), McGuffog, L. (Lesley), Mulligan, A.M. (Anna Marie), Andrulis, I.L. (Irene), Spurdle, A.B. (Amanda), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Engel, C. (Christoph), Wapenschmidt, B. (Barbara), Nevanlinna, H. (Heli), Thomassen, M. (Mads), Southey, M.C. (Melissa), Radice, P. (Paolo), Ramus, S.J. (Susan), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Lee, A. (Andrew), Healey, S. (Sue), Nussbaum, R. (Robert), Rebbeck, R. (Timothy), Arun, B.K. (Banu), James, M. (Margaret), Karlan, B.Y. (Beth), Lester, K.J. (Kathryn), Cass, I. (Ilana), Terry, M.B. (Mary Beth), Daly, M.J. (Mark), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Overeem Hansen, T. (Thomas) van, Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Nielsen, F. (Finn), Dennis, J. (Joe), Cunningham, J.M. (Julie), Hart, S. (Stewart), Slager, S. (Susan), Osorio, A. (Ana), Benítez, J. (Javier), Duran, M. (Mercedes), Weitzel, J.N. (Jeffrey), Tafur, I. (Isaac), Hander, M. (Mary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Roversi, G. (Gaia), Scuvera, G. (Giulietta), Bonnani, B. (Bernardo), Mariani, P. (Paolo), Volorio, S. (Sara), Dolcetti, R. (Riccardo), Varesco, L. (Liliana), Papi, L. (Laura), Tibiletti, M.G. (Maria Grazia), Giannini, G. (Giuseppe), Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J. (Judy), Hamann, U. (Ute), Donaldson, A. (Alan), Brewer, C. (Carole), Foo, C. (Claire), Evans, D.G. (Gareth), Frost, D. (Debra), Eccles, D. (Diana), Douglas, F. (Fiona), Brady, A. (A.), Cook, J. (Jackie), Tischkowitz, M. (Marc), Adlard, L., Barwell, J. (Julian), Ong, K., Walker, L.J. (Lisa), Izatt, L. (Louise), Side, L. (Lucy), Kennedy, M.J. (John), Rogers, M.T. (Mark), Porteous, M.E. (Mary), Morrison, P.J. (Patrick), Platte, R. (Radka), Eeles, R. (Ros), Davidson, R. (Rosemarie), Hodgson, S. (Shirley), Ellis, S.D. (Steve), Godwin, A.K. (Andrew), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Steinemann, D. (Doris), Bogdanova-Markov, N. (Nadja), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Wang-Gohrke, S. (Shan), Gehrig, P.A. (Paola A.), Markiefka, B. (Birgid), Buecher, B. (Bruno), Lefol, C. (Cédrick), Stoppa-Lyonnet, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Barjhoux, L. (Laure), Faivre, L. (Laurence), Longy, M. (Michel), Sevenet, N. (Nicolas), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Bonadona, V. (Valérie), Caux-Moncoutier, V. (Virginie), Isaacs, C. (Claudine), Van Maerken, T. (Tom), Claes, K.B.M. (Kathleen B.M.), Piedmonte, M. (Marion), Andrews, L. (Lesley), Hays, J. (John), Rodriguez, G.C. (Gustavo), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Khan, S. (Sofia), Hogervorst, F.B.L. (Frans), Aalfs, C.M. (Cora), Lange, J.L. (J.) de, Meijers-Heijboer, E.J. (Hanne), Hout, A.H. (Annemarie) van der, Wijnen, J.T. (Juul), Roozendaal, K.E. (Kees) van, Mensenkamp, A.R. (Arjen), Ouweland, A.M.W. (Ans) van den, Deurzen, C.H.M. (Carolien) van, Luijt, R.B. (Rob) van der, Olah, E., Díez, O. (Orland), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Teulé, A. (A.), Menéndez, M. (Mireia), Jakubowska, A. (Anna), Lubinski, J. (Jan), Cybulski, C. (Cezary), Gronwald, J. (Jacek), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Arason, A. (Adalgeir), Maugard, C., Soucy, P. (Penny), Montagna, M. (Marco), Agata, S. (Simona), Teixeira, P.J., Olswold, C. (Curtis), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Hallberg, B. (Boubou), Wang, X. (Xianshu), Szabo, C. (Csilla), Vijai, J. (Joseph), Jacobs, L. (Lauren), Corines, M. (Marina), Lincoln, A. (Anne), Berger, A. (Andreas), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Kaulich, D.G. (Daphne Gschwantler), Pfeiler, G. (Georg), Tea, M.-K., Phelan, C. (Catherine), Mai, P.L. (Phuong), Greene, M.H. (Mark), Rennert, G. (Gad), Imyanitov, E.N. (Evgeny), Glendon, G. (Gord), Toland, A.E. (Amanda), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Jensen, U.B., Caligo, M.A. (Maria), Friedman, E. (Eitan), Berger, R. (Raanan), Laitman, Y. (Yael), Rantala, J. (Johanna), Arver, B. (Brita Wasteson), Loman, N. (Niklas), Borg, Å. (Åke), Ehrencrona, H. (Hans), Olopade, O.I. (Olofunmilayo), Simard, J. (Jacques), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis), Kuchenbaecker, K.B. (Karoline), Neuhausen, S.L. (Susan), Robson, M. (Mark), Barrowdale, D. (Daniel), McGuffog, L. (Lesley), Mulligan, A.M. (Anna Marie), Andrulis, I.L. (Irene), Spurdle, A.B. (Amanda), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Engel, C. (Christoph), Wapenschmidt, B. (Barbara), Nevanlinna, H. (Heli), Thomassen, M. (Mads), Southey, M.C. (Melissa), Radice, P. (Paolo), Ramus, S.J. (Susan), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Lee, A. (Andrew), Healey, S. (Sue), Nussbaum, R. (Robert), Rebbeck, R. (Timothy), Arun, B.K. (Banu), James, M. (Margaret), Karlan, B.Y. (Beth), Lester, K.J. (Kathryn), Cass, I. (Ilana), Terry, M.B. (Mary Beth), Daly, M.J. (Mark), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Overeem Hansen, T. (Thomas) van, Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Nielsen, F. (Finn), Dennis, J. (Joe), Cunningham, J.M. (Julie), Hart, S. (Stewart), Slager, S. (Susan), Osorio, A. (Ana), Benítez, J. (Javier), Duran, M. (Mercedes), Weitzel, J.N. (Jeffrey), Tafur, I. (Isaac), Hander, M. (Mary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Roversi, G. (Gaia), Scuvera, G. (Giulietta), Bonnani, B. (Bernardo), Mariani, P. (Paolo), Volorio, S. (Sara), Dolcetti, R. (Riccardo), Varesco, L. (Liliana), Papi, L. (Laura), Tibiletti, M.G. (Maria Grazia), Giannini, G. (Giuseppe), Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J. (Judy), Hamann, U. (Ute), Donaldson, A. (Alan), Brewer, C. (Carole), Foo, C. (Claire), Evans, D.G. (Gareth), Frost, D. (Debra), Eccles, D. (Diana), Douglas, F. (Fiona), Brady, A. (A.), Cook, J. (Jackie), Tischkowitz, M. (Marc), Adlard, L., Barwell, J. (Julian), Ong, K., Walker, L.J. (Lisa), Izatt, L. (Louise), Side, L. (Lucy), Kennedy, M.J. (John), Rogers, M.T. (Mark), Porteous, M.E. (Mary), Morrison, P.J. (Patrick), Platte, R. (Radka), Eeles, R. (Ros), Davidson, R. (Rosemarie), Hodgson, S. (Shirley), Ellis, S.D. (Steve), Godwin, A.K. (Andrew), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Steinemann, D. (Doris), Bogdanova-Markov, N. (Nadja), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Wang-Gohrke, S. (Shan), Gehrig, P.A. (Paola A.), Markiefka, B. (Birgid), Buecher, B. (Bruno), Lefol, C. (Cédrick), Stoppa-Lyonnet, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Barjhoux, L. (Laure), Faivre, L. (Laurence), Longy, M. (Michel), Sevenet, N. (Nicolas), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Bonadona, V. (Valérie), Caux-Moncoutier, V. (Virginie), Isaacs, C. (Claudine), Van Maerken, T. (Tom), Claes, K.B.M. (Kathleen B.M.), Piedmonte, M. (Marion), Andrews, L. (Lesley), Hays, J. (John), Rodriguez, G.C. (Gustavo), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Khan, S. (Sofia), Hogervorst, F.B.L. (Frans), Aalfs, C.M. (Cora), Lange, J.L. (J.) de, Meijers-Heijboer, E.J. (Hanne), Hout, A.H. (Annemarie) van der, Wijnen, J.T. (Juul), Roozendaal, K.E. (Kees) van, Mensenkamp, A.R. (Arjen), Ouweland, A.M.W. (Ans) van den, Deurzen, C.H.M. (Carolien) van, Luijt, R.B. (Rob) van der, Olah, E., Díez, O. (Orland), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Teulé, A. (A.), Menéndez, M. (Mireia), Jakubowska, A. (Anna), Lubinski, J. (Jan), Cybulski, C. (Cezary), Gronwald, J. (Jacek), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Arason, A. (Adalgeir), Maugard, C., Soucy, P. (Penny), Montagna, M. (Marco), Agata, S. (Simona), Teixeira, P.J., Olswold, C. (Curtis), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Hallberg, B. (Boubou), Wang, X. (Xianshu), Szabo, C. (Csilla), Vijai, J. (Joseph), Jacobs, L. (Lauren), Corines, M. (Marina), Lincoln, A. (Anne), Berger, A. (Andreas), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Kaulich, D.G. (Daphne Gschwantler), Pfeiler, G. (Georg), Tea, M.-K., Phelan, C. (Catherine), Mai, P.L. (Phuong), Greene, M.H. (Mark), Rennert, G. (Gad), Imyanitov, E.N. (Evgeny), Glendon, G. (Gord), Toland, A.E. (Amanda), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Jensen, U.B., Caligo, M.A. (Maria), Friedman, E. (Eitan), Berger, R. (Raanan), Laitman, Y. (Yael), Rantala, J. (Johanna), Arver, B. (Brita Wasteson), Loman, N. (Niklas), Borg, Å. (Åke), Ehrencrona, H. (Hans), Olopade, O.I. (Olofunmilayo), Simard, J. (Jacques), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Couch, F.J. (Fergus), and Antoniou, A.C. (Antonis)
Abstract: Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive ass
Published: 2014
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55. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Author: Kuchenbaecker, KB, Neuhausen, SL, Robson, M, Barrowdale, D, McGuffog, L, Mulligan, AM, Andrulis, IL, Spurdle, AB, Schmidt, MK, Schmutzler, RK, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, SJ, Domchek, SM, Nathanson, KL, Lee, A, Healey, S, Nussbaum, RL, Rebbeck, TR, Arun, BK, James, P, Karlan, BY, Lester, J, Cass, I, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, CM, van Rensburg, EJ, Steele, L, Hansen, TVO, Ejlertsen, B, Gerdes, A-M, Nielsen, FC, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, JN, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, MG, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, DG, Frost, D, Eccles, D, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K-R, Walker, L, Izatt, L, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, AK, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova-Markov, N, Kast, K, Varon-Mateeva, R, Wang-Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa-Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, OM, Mazoyer, S, Bonadona, V, Caux-Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, GC, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, FBL, Aalfs, CM, de lange, JL, Meijers-Heijboer, HEJ, van der Hout, AH, Wijnen, JT, van Roozendaal, KEP, Mensenkamp, AR, van den Ouweland, AMW, van Deurzen, CHM, van der Luijt, RB, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teule, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska-Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, MR, Olswold, C, Lindor, N, Pankratz, VS, Hallberg, E, Wang, X, Szabo, CI, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Kaulich, DG, Pfeiler, G, Tea, M-K, Phelan, CM, Mai, PL, Greene, MH, Rennert, G, Imyanitov, EN, Glendon, G, Toland, AE, Bojesen, A, Pedersen, IS, Jensen, UB, Caligo, MA, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, OI, Simard, J, Easton, DF, Chenevix-Trench, G, Offit, K, Couch, FJ, Antoniou, AC, Kuchenbaecker, KB, Neuhausen, SL, Robson, M, Barrowdale, D, McGuffog, L, Mulligan, AM, Andrulis, IL, Spurdle, AB, Schmidt, MK, Schmutzler, RK, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, SJ, Domchek, SM, Nathanson, KL, Lee, A, Healey, S, Nussbaum, RL, Rebbeck, TR, Arun, BK, James, P, Karlan, BY, Lester, J, Cass, I, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, CM, van Rensburg, EJ, Steele, L, Hansen, TVO, Ejlertsen, B, Gerdes, A-M, Nielsen, FC, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, JN, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, MG, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, DG, Frost, D, Eccles, D, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K-R, Walker, L, Izatt, L, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, AK, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova-Markov, N, Kast, K, Varon-Mateeva, R, Wang-Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa-Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, OM, Mazoyer, S, Bonadona, V, Caux-Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, GC, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, FBL, Aalfs, CM, de lange, JL, Meijers-Heijboer, HEJ, van der Hout, AH, Wijnen, JT, van Roozendaal, KEP, Mensenkamp, AR, van den Ouweland, AMW, van Deurzen, CHM, van der Luijt, RB, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teule, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska-Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, MR, Olswold, C, Lindor, N, Pankratz, VS, Hallberg, E, Wang, X, Szabo, CI, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Kaulich, DG, Pfeiler, G, Tea, M-K, Phelan, CM, Mai, PL, Greene, MH, Rennert, G, Imyanitov, EN, Glendon, G, Toland, AE, Bojesen, A, Pedersen, IS, Jensen, UB, Caligo, MA, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, OI, Simard, J, Easton, DF, Chenevix-Trench, G, Offit, K, Couch, FJ, and Antoniou, AC
Abstract: INTRODUCTION: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. METHODS: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. RESULTS: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10(-6) in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement
Published: 2014

56. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Author: Kuchenbaecker, K, Neuhausen, S, Robson, M, Barrowdale, D, Mcguffog, L, Mulligan, A, Andrulis, I, Spurdle, A, Schmidt, M, Schmutzler, R, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, S, Domchek, S, Nathanson, K, Lee, A, Healey, S, Nussbaum, R, Rebbeck, T, Arun, B, James, P, Karlan, B, Lester, J, Cass, I, Breast Cancer Family, R, Terry, M, Daly, M, Goldgar, D, Buys, S, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, C, van Rensburg, E, Steele, L, v. O. Hansen, T, Ejlertsen, B, Gerdes, A, Nielsen, F, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, J, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, M, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, D, Frost, D, Eccles, D, Embrace, S, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K, Walker, L, Izatt, L, Side, L, Kennedy, M, Rogers, M, Porteous, M, Morrison, P, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, A, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova Markov, N, Kast, K, Varon Mateeva, R, Wang Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, GEMO Study, C, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, O, Mazoyer, S, Bonadona, V, Caux Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, G, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, F, Aalfs, C, de Lange, J, Meijers Heijboer, H, van der Hout, A, Wijnen, J, van Roozendaal, K, Mensenkamp, A, van den Ouweland, A, van Deurzen, C, van der Luijt, R, Hebon, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teulé, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, M, Kconfab, I, Olswold, C, Lindor, N, Pankratz, V, Hallberg, E, Wang, X, Szabo, C, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink Retter, A, Singer, C, Rappaport, C, Kaulich, D, Pfeiler, G, Tea, M, Phelan, C, Mai, P, Greene, M, Rennert, G, Imyanitov, E, Glendon, G, Toland, A, Bojesen, A, Pedersen, I, Jensen, U, Caligo, M, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, O, Simard, J, Easton, D, Chenevix Trench, G, Offit, K, Couch, F, Antoniou, A, Cimba, Kuchenbaecker, KB, Neuhausen, SL, McGuffog, L, Mulligan, AM, Andrulis, IL, Spurdle, AB, Schmidt, MK, Schmutzler, RK, Ramus, SJ, Domchek, SM, Nathanson, KL, Nussbaum, RL, Rebbeck, TR, Arun, BK, Karlan, BY, Breast Cancer Family Registry, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Dorfling, CM, van Rensburg, EJ, Gerdes, AM, Nielsen, FC, Weitzel, JN, ROVERSI, GAIA, Tibiletti, MG, Evans, DG, EMBRACE Study, Ong, KR, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Godwin, AK, GEMO Study Collaborators, Sinilnikova, OM, Rodriguez, GC, Hogervorst, FB, Aalfs, CM, de Lange, JL, Meijers Heijboer, HE, van der Hout, AH, Wijnen, JT, van Roozendaal, KE, Mensenkamp, AR, van den Ouweland, AM, van Deurzen, CH, van der Luijt, RB, HEBON, Teixeira, MR, KConFab, Investigators, Pankratz, VS, Szabo, CI, Singer, CF, Kaulich, DG, Tea, MK, Phelan, CM, Mai, PL, Greene, MH, Imyanitov, EN, Toland, AE, Pedersen, IS, Jensen, UB, Caligo, MA, Olopade, OI, Easton, DF, Couch, FJ, Antoniou, AC, CIMBA, Kuchenbaecker, K, Neuhausen, S, Robson, M, Barrowdale, D, Mcguffog, L, Mulligan, A, Andrulis, I, Spurdle, A, Schmidt, M, Schmutzler, R, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, S, Domchek, S, Nathanson, K, Lee, A, Healey, S, Nussbaum, R, Rebbeck, T, Arun, B, James, P, Karlan, B, Lester, J, Cass, I, Breast Cancer Family, R, Terry, M, Daly, M, Goldgar, D, Buys, S, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, C, van Rensburg, E, Steele, L, v. O. Hansen, T, Ejlertsen, B, Gerdes, A, Nielsen, F, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, J, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, M, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, D, Frost, D, Eccles, D, Embrace, S, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K, Walker, L, Izatt, L, Side, L, Kennedy, M, Rogers, M, Porteous, M, Morrison, P, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, A, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova Markov, N, Kast, K, Varon Mateeva, R, Wang Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, GEMO Study, C, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, O, Mazoyer, S, Bonadona, V, Caux Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, G, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, F, Aalfs, C, de Lange, J, Meijers Heijboer, H, van der Hout, A, Wijnen, J, van Roozendaal, K, Mensenkamp, A, van den Ouweland, A, van Deurzen, C, van der Luijt, R, Hebon, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teulé, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, M, Kconfab, I, Olswold, C, Lindor, N, Pankratz, V, Hallberg, E, Wang, X, Szabo, C, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink Retter, A, Singer, C, Rappaport, C, Kaulich, D, Pfeiler, G, Tea, M, Phelan, C, Mai, P, Greene, M, Rennert, G, Imyanitov, E, Glendon, G, Toland, A, Bojesen, A, Pedersen, I, Jensen, U, Caligo, M, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, O, Simard, J, Easton, D, Chenevix Trench, G, Offit, K, Couch, F, Antoniou, A, Cimba, Kuchenbaecker, KB, Neuhausen, SL, McGuffog, L, Mulligan, AM, Andrulis, IL, Spurdle, AB, Schmidt, MK, Schmutzler, RK, Ramus, SJ, Domchek, SM, Nathanson, KL, Nussbaum, RL, Rebbeck, TR, Arun, BK, Karlan, BY, Breast Cancer Family Registry, Terry, MB, Daly, MB, Goldgar, DE, Buys, SS, Dorfling, CM, van Rensburg, EJ, Gerdes, AM, Nielsen, FC, Weitzel, JN, ROVERSI, GAIA, Tibiletti, MG, Evans, DG, EMBRACE Study, Ong, KR, Side, LE, Kennedy, MJ, Rogers, MT, Porteous, ME, Morrison, PJ, Godwin, AK, GEMO Study Collaborators, Sinilnikova, OM, Rodriguez, GC, Hogervorst, FB, Aalfs, CM, de Lange, JL, Meijers Heijboer, HE, van der Hout, AH, Wijnen, JT, van Roozendaal, KE, Mensenkamp, AR, van den Ouweland, AM, van Deurzen, CH, van der Luijt, RB, HEBON, Teixeira, MR, KConFab, Investigators, Pankratz, VS, Szabo, CI, Singer, CF, Kaulich, DG, Tea, MK, Phelan, CM, Mai, PL, Greene, MH, Imyanitov, EN, Toland, AE, Pedersen, IS, Jensen, UB, Caligo, MA, Olopade, OI, Easton, DF, Couch, FJ, Antoniou, AC, and CIMBA
Abstract: Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC)=0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC=0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC=0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10-6 in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement. Con
Published: 2014

57. 943P - Location of mutation in BRCA2 gene and survival in patients with ovarian cancer

Author: Labidi-Galy, S.I., Olivier, T., Rodrigues, M., Ferraioli, D., Derbel, O., Bodmer, A., Petignat, P., Chopin, N., Tredan, O., Heudel, P., Viassolo, V., Ayme, A., Chappuis, P.O., Stern, M-H., Houdayer, C., Stoppa-Lyonnet, D., Buisson, A., Golmard, L., Bonadona, V., and Ray-Coquard, I.
Published: 2017
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58. GermlineBAP1mutations predispose also to multiple basal cell carcinomas

Author: de la Fouchardière, A., primary, Cabaret, O., additional, Savin, L., additional, Combemale, P., additional, Schvartz, H., additional, Penet, C., additional, Bonadona, V., additional, Soufir, N., additional, and Bressac-de Paillerets, B., additional
Published: 2014
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59. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers

Author: Phillips, K.-A. (Kelly-Anne), Milne, R.L. (Roger), Rookus, M.A. (Matti), Daly, M.J. (Mark), Antoniou, A.C. (Antonis), Peock, S. (Susan), Frost, D. (Debra), Easton, D.F. (Douglas), Ellis, S.D. (Steve), Friedlander, M. (Michael), Buys, S.S. (Saundra), Andrieu, N. (Nadine), Nogues, C. (Catherine), Stoppa-Lyonnet, D. (Dominique), Bonadona, V. (Valérie), Pujol, P. (Pascal), McLachlan, S.-A. (Sue-Anne), John, E.M. (Esther), Hooning, M.J. (Maartje), Seynaeve, C.M. (Caroline), Tollenaar, R.A.E.M. (Rob), Goldgar, D. (David), Terry, M.B. (Mary Beth), Caldes, T. (Trinidad), Weideman, P.C. (Prue C.), Andrulis, I.L. (Irene), Singer, C.F. (Christian), Birch, K. (Kate), Simard, J. (Jacques), Southey, M.C. (Melissa), Olsson, H.L. (Håkan L.), Jakubowska, A. (Anna), Olah, E., Gerdes, A-M. (Anne-Marie), Foretova, L. (Lenka), Hopper, J.L. (John), Phillips, K.-A. (Kelly-Anne), Milne, R.L. (Roger), Rookus, M.A. (Matti), Daly, M.J. (Mark), Antoniou, A.C. (Antonis), Peock, S. (Susan), Frost, D. (Debra), Easton, D.F. (Douglas), Ellis, S.D. (Steve), Friedlander, M. (Michael), Buys, S.S. (Saundra), Andrieu, N. (Nadine), Nogues, C. (Catherine), Stoppa-Lyonnet, D. (Dominique), Bonadona, V. (Valérie), Pujol, P. (Pascal), McLachlan, S.-A. (Sue-Anne), John, E.M. (Esther), Hooning, M.J. (Maartje), Seynaeve, C.M. (Caroline), Tollenaar, R.A.E.M. (Rob), Goldgar, D. (David), Terry, M.B. (Mary Beth), Caldes, T. (Trinidad), Weideman, P.C. (Prue C.), Andrulis, I.L. (Irene), Singer, C.F. (Christian), Birch, K. (Kate), Simard, J. (Jacques), Southey, M.C. (Melissa), Olsson, H.L. (Håkan L.), Jakubowska, A. (Anna), Olah, E., Gerdes, A-M. (Anne-Marie), Foretova, L. (Lenka), and Hopper, J.L. (John)
Abstract: Purpose To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers. Methods Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up. Results Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC di
Published: 2013
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60. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

Author: Couch, F.J. (Fergus), McGuffog, L. (Lesley), Lee, A. (Andrew), Olswold, C. (Curtis), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Fredericksen, Z. (Zachary), Barrowdale, D. (Daniel), Dennis, J. (Joe), Gaudet, M.M. (Mia), Dicks, E. (Ed), Kosel, M. (Matthew), Healey, S. (Sue), Sinilnikova, O. (Olga), Bacot, F. (Francois), Vincent, D. (Daniel), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Jakubowska, A. (Anna), Radice, P. (Paolo), Schmutzler, R.K. (Rita), Domchek, S.M. (Susan), Piedmonte, M. (Marion), Singer, C.F. (Christian), Friedman, E. (Eitan), Thomassen, M. (Mads), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Szabo, C. (Csilla), Blanco, I. (Ignacio), Greene, M.H. (Mark), Karlan, B.Y. (Beth), Garber, J., Phelan, C. (Catherine), Weitzel, J.N. (Jeffrey), Montagna, M. (Marco), Olah, E., Andrulis, I.L. (Irene), Godwin, A.K. (Andrew), Yannoukakos, D. (Drakoulis), Goldgar, D. (David), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Terry, M.-B. (Mary-Beth), Daly, M.B. (Mary), Rensburg, E.J. (Elizabeth) van, Hamann, U. (Ute), Ramus, S.J. (Susan), Ewart-Toland, A. (Amanda), Caligo, M.A. (Maria), Olopade, O.I. (Olofunmilayo), Tung, N. (Nadine), Claes, K. (Kathleen), Beattie, M.S. (Mary), Southey, M.C. (Melissa), Imyanitov, E.N. (Evgeny), Tischkowitz, M. (Marc), Janavicius, R. (Ramunas), John, E.M. (Esther), Kwong, A. (Ava), Diez, O. (Orland), Balmana, J. (Judith), Barkardottir, R.B. (Rosa), Arun, B.K. (Banu), Rennert, G. (Gad), Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Campbell, I. (Ian), Hout, A.H. (Annemarie) van der, Deurzen, C.H.M. (Carolien) van, Seynaeve, C.M. (Caroline), Gómez García, E.B. (Encarna), Leeuwen, F.E. (Flora) van, Meijers-Heijboer, H. (Hanne), Gille, J.J. (Johan), Ausems, M.G.E.M. (Margreet), Blok, M.J. (Marinus), Ligtenberg, M.J. (Marjolijn), Rookus, M.A. (Matti), Devilee, P. (Peter), Verhoef, S., Os, T.A.M. (Theo) van, Wijnen, J.T. (Juul), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Eccles, D. (Diana), Cook, J. (Jackie), Brewer, C. (C.), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Side, L. (Lucy), Donaldson, A. (Alan), Houghton, C. (Catherine), Rogers, M.T. (Mark), Dorkins, H. (Huw), Eason, J. (Jacqueline), Gregory, H. (Helen), McCann, E. (Emma), Murray, A. (Alexandra), Calender, A. (Alain), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Delnatte, C.D. (Capucine), Nogues, C. (Catherine), Lasset, C. (Christine), Houdayer, C. (Claude), Leroux, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Sobol, H. (Hagay), Coupier, I. (Isabelle), Vénat-Bouvet, L. (Laurence), Castera, L. (Laurent), Gauthier-Villars, M. (Marion), Léone, M. (Mélanie), Pujol, P. (Pascal), Mazoyer, S. (Sylvie), Bignon, Y.-J. (Yves-Jean), Złowocka-Perłowska, E. (Elzbieta), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska, K. (Katarzyna), Huzarski, T. (Tomasz), Spurdle, A.B. (Amanda), Viel, A. (Alessandra), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Melloni, G. (Giulia), Ottini, L. (Laura), Papi, L. (Laura), Varesco, L. (Liliana), Tibiletti, M.G. (Maria Grazia), Peterlongo, P. (Paolo), Volorio, S. (Sara), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Arnold, N. (Norbert), Engel, C. (Christoph), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Gehrig, P.A. (Paola A.), Kast, K. (Karin), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Niederacher, D. (Dieter), Ditsch, N. (Nina), Plendl, H. (Hansjoerg), Preisler-Adams, S. (Sabine), Engert, S. (Stefanie), Sutter, C. (Christian), Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Weber, B.H.F. (Bernhard), Arver, B. (Brita Wasteson), Stenmark-Askmalm, M. (M.), Loman, N. (Niklas), Rosenquist, R. (R.), Einbeigi, Z. (Zakaria), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Blank, S.V. (Stephanie), Cohn, D.E. (David), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Friedlander, M. (Michael), Bae-Jump, V.L. (Victoria L.), Fink-Retter, A. (Anneliese), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Lindor, N.M. (Noralane), Kaufman, B. (Bella), Shimon Paluch, S. (Shani), Laitman, Y. (Yael), Skytte, A.-B. (Anne-Bine), Gerdes, A-M. (Anne-Marie), Pedersen, I.S. (Inge Sokilde), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Vijai, J. (Joseph), Sarrel, K. (Kara), Robson, M. (Mark), Kauff, N. (Noah), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Ejlertsen, B. (Bent), Nielsen, F.C. (Finn), Jønson, L. (Lars), Andersen, M.K. (Mette), Ding, Y.C. (Yuan), Steele, L. (Linda), Foretova, L. (Lenka), Teulé, A. (A.), Lázaro, C. (Conxi), Brunet, J. (Joan), Pujana, M.A. (Miguel), Mai, P.L. (Phuong), Loud, J.T. (Jennifer), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Orsulic, S. (Sandra), Narod, S. (Steven), Herzog, J. (Josef), Sand, S.R. (Sharon), Tognazzo, S. (Silvia), Agata, S. (Simona), Vaszko, T. (Tibor), Weaver, J. (JoEllen), Stavropoulou, A. (Alexandra), Buys, S.S. (Saundra), Romero, A. (Alfonso), Hoya, M. (Miguel) de La, Aittomäki, K. (Kristiina), Muranen, T.A. (Taru), Durán, M. (Mercedes), Chung, W.K. (Wendy), Lasa, A. (Adriana), Dorfling, C.M. (Cecelia), Miron, A. (Alexander), Benítez, J. (Javier), Senter, L. (Leigha), Huo, D. (Dezheng), Chan, S. (Salina), Sokolenko, A. (Anna), Chiquette, J. (Jocelyne), Tihomirova, L. (Laima), Friebel, M.O.W. (Mark ), Agnarsson, B.A. (Bjarni), Lu, K.H. (Karen), Lejbkowicz, F. (Flavio), James, P.A. (Paul ), Hall, A.S. (Alistair), Dunning, A.M. (Alison), Tessier, Y. (Yann), Cunningham, J. (Jane), Slager, S. (Susan), Wang, C. (Chen), Hart, S. (Stewart), Stevens, K. (Kristen), Simard, J. (Jacques), Pastinen, T. (Tomi), Pankratz, V.S. (Shane), Offit, K. (Kenneth), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Thorne, H. (Heather), Niedermayr, E. (Eveline), Borg, Å. (Åke), Olsson, H., Jernström, H. (H.), Henriksson, K. (Karin), Harbst, K. (Katja), Soller, M. (Maria), Kristoffersson, U. (Ulf), Wang, X. (Xianshu), Öfverholm, A. (Anna), Nordling, M. (Margareta), Karlsson, P. (Per), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Lindblom, A. (Annika), Bustinza, G.B., Rantala, J. (Johanna), Melin, B. (Beatrice), Ardnor, C.E. (Christina Edwinsdotter), Emanuelsson, M. (Monica), Ehrencrona, H. (Hans), Pigg, M.H. (Maritta ), Liedgren, S. (Sigrun), Rookus, M.A. (M.), Verhoef, S. (S.), Schmidt, M.K. (Marjanka), Lange, J.L. (J.) de, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Aalfs, C.M. (Cora), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gomez Garcia, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Anna), Kennedy, M.J. (John), Barton, D.E. (David), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Brady, A.F. (Angela), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Lalloo, F. (Fiona), Taylor, J. (James), Male, A. (Alison), Berlin, C. (Cheryl), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Stormorken, A. (Astrid), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Buecher, B. (Bruno), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Uhrhammer, N. (Nancy), Bonadona, V. (Valérie), Handallou, S. (Sandrine), hardouin, A. (Agnès), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Lidereau, R. (Rosette), Demange, L. (Liliane), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Frenay, M. (Marc), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Sokolowska, J. (Johanna), Bronner, M. (Myriam), Lynch, H. (Henry), Snyder, C.L. (Carrie), Angelakos, M. (Maggie), Maskiell, J. (Judi), Dite, G.S. (Gillian), Couch, F.J. (Fergus), McGuffog, L. (Lesley), Lee, A. (Andrew), Olswold, C. (Curtis), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Fredericksen, Z. (Zachary), Barrowdale, D. (Daniel), Dennis, J. (Joe), Gaudet, M.M. (Mia), Dicks, E. (Ed), Kosel, M. (Matthew), Healey, S. (Sue), Sinilnikova, O. (Olga), Bacot, F. (Francois), Vincent, D. (Daniel), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Jakubowska, A. (Anna), Radice, P. (Paolo), Schmutzler, R.K. (Rita), Domchek, S.M. (Susan), Piedmonte, M. (Marion), Singer, C.F. (Christian), Friedman, E. (Eitan), Thomassen, M. (Mads), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Szabo, C. (Csilla), Blanco, I. (Ignacio), Greene, M.H. (Mark), Karlan, B.Y. (Beth), Garber, J., Phelan, C. (Catherine), Weitzel, J.N. (Jeffrey), Montagna, M. (Marco), Olah, E., Andrulis, I.L. (Irene), Godwin, A.K. (Andrew), Yannoukakos, D. (Drakoulis), Goldgar, D. (David), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Terry, M.-B. (Mary-Beth), Daly, M.B. (Mary), Rensburg, E.J. (Elizabeth) van, Hamann, U. (Ute), Ramus, S.J. (Susan), Ewart-Toland, A. (Amanda), Caligo, M.A. (Maria), Olopade, O.I. (Olofunmilayo), Tung, N. (Nadine), Claes, K. (Kathleen), Beattie, M.S. (Mary), Southey, M.C. (Melissa), Imyanitov, E.N. (Evgeny), Tischkowitz, M. (Marc), Janavicius, R. (Ramunas), John, E.M. (Esther), Kwong, A. (Ava), Diez, O. (Orland), Balmana, J. (Judith), Barkardottir, R.B. (Rosa), Arun, B.K. (Banu), Rennert, G. (Gad), Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Campbell, I. (Ian), Hout, A.H. (Annemarie) van der, Deurzen, C.H.M. (Carolien) van, Seynaeve, C.M. (Caroline), Gómez García, E.B. (Encarna), Leeuwen, F.E. (Flora) van, Meijers-Heijboer, H. (Hanne), Gille, J.J. (Johan), Ausems, M.G.E.M. (Margreet), Blok, M.J. (Marinus), Ligtenberg, M.J. (Marjolijn), Rookus, M.A. (Matti), Devilee, P. (Peter), Verhoef, S., Os, T.A.M. (Theo) van, Wijnen, J.T. (Juul), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Eccles, D. (Diana), Cook, J. (Jackie), Brewer, C. (C.), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Side, L. (Lucy), Donaldson, A. (Alan), Houghton, C. (Catherine), Rogers, M.T. (Mark), Dorkins, H. (Huw), Eason, J. (Jacqueline), Gregory, H. (Helen), McCann, E. (Emma), Murray, A. (Alexandra), Calender, A. (Alain), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Delnatte, C.D. (Capucine), Nogues, C. (Catherine), Lasset, C. (Christine), Houdayer, C. (Claude), Leroux, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Sobol, H. (Hagay), Coupier, I. (Isabelle), Vénat-Bouvet, L. (Laurence), Castera, L. (Laurent), Gauthier-Villars, M. (Marion), Léone, M. (Mélanie), Pujol, P. (Pascal), Mazoyer, S. (Sylvie), Bignon, Y.-J. (Yves-Jean), Złowocka-Perłowska, E. (Elzbieta), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska, K. (Katarzyna), Huzarski, T. (Tomasz), Spurdle, A.B. (Amanda), Viel, A. (Alessandra), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Melloni, G. (Giulia), Ottini, L. (Laura), Papi, L. (Laura), Varesco, L. (Liliana), Tibiletti, M.G. (Maria Grazia), Peterlongo, P. (Paolo), Volorio, S. (Sara), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Arnold, N. (Norbert), Engel, C. (Christoph), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Gehrig, P.A. (Paola A.), Kast, K. (Karin), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Niederacher, D. (Dieter), Ditsch, N. (Nina), Plendl, H. (Hansjoerg), Preisler-Adams, S. (Sabine), Engert, S. (Stefanie), Sutter, C. (Christian), Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Weber, B.H.F. (Bernhard), Arver, B. (Brita Wasteson), Stenmark-Askmalm, M. (M.), Loman, N. (Niklas), Rosenquist, R. (R.), Einbeigi, Z. (Zakaria), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Blank, S.V. (Stephanie), Cohn, D.E. (David), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Friedlander, M. (Michael), Bae-Jump, V.L. (Victoria L.), Fink-Retter, A. (Anneliese), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Lindor, N.M. (Noralane), Kaufman, B. (Bella), Shimon Paluch, S. (Shani), Laitman, Y. (Yael), Skytte, A.-B. (Anne-Bine), Gerdes, A-M. (Anne-Marie), Pedersen, I.S. (Inge Sokilde), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Vijai, J. (Joseph), Sarrel, K. (Kara), Robson, M. (Mark), Kauff, N. (Noah), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Ejlertsen, B. (Bent), Nielsen, F.C. (Finn), Jønson, L. (Lars), Andersen, M.K. (Mette), Ding, Y.C. (Yuan), Steele, L. (Linda), Foretova, L. (Lenka), Teulé, A. (A.), Lázaro, C. (Conxi), Brunet, J. (Joan), Pujana, M.A. (Miguel), Mai, P.L. (Phuong), Loud, J.T. (Jennifer), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Orsulic, S. (Sandra), Narod, S. (Steven), Herzog, J. (Josef), Sand, S.R. (Sharon), Tognazzo, S. (Silvia), Agata, S. (Simona), Vaszko, T. (Tibor), Weaver, J. (JoEllen), Stavropoulou, A. (Alexandra), Buys, S.S. (Saundra), Romero, A. (Alfonso), Hoya, M. (Miguel) de La, Aittomäki, K. (Kristiina), Muranen, T.A. (Taru), Durán, M. (Mercedes), Chung, W.K. (Wendy), Lasa, A. (Adriana), Dorfling, C.M. (Cecelia), Miron, A. (Alexander), Benítez, J. (Javier), Senter, L. (Leigha), Huo, D. (Dezheng), Chan, S. (Salina), Sokolenko, A. (Anna), Chiquette, J. (Jocelyne), Tihomirova, L. (Laima), Friebel, M.O.W. (Mark ), Agnarsson, B.A. (Bjarni), Lu, K.H. (Karen), Lejbkowicz, F. (Flavio), James, P.A. (Paul ), Hall, A.S. (Alistair), Dunning, A.M. (Alison), Tessier, Y. (Yann), Cunningham, J. (Jane), Slager, S. (Susan), Wang, C. (Chen), Hart, S. (Stewart), Stevens, K. (Kristen), Simard, J. (Jacques), Pastinen, T. (Tomi), Pankratz, V.S. (Shane), Offit, K. (Kenneth), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Thorne, H. (Heather), Niedermayr, E. (Eveline), Borg, Å. (Åke), Olsson, H., Jernström, H. (H.), Henriksson, K. (Karin), Harbst, K. (Katja), Soller, M. (Maria), Kristoffersson, U. (Ulf), Wang, X. (Xianshu), Öfverholm, A. (Anna), Nordling, M. (Margareta), Karlsson, P. (Per), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Lindblom, A. (Annika), Bustinza, G.B., Rantala, J. (Johanna), Melin, B. (Beatrice), Ardnor, C.E. (Christina Edwinsdotter), Emanuelsson, M. (Monica), Ehrencrona, H. (Hans), Pigg, M.H. (Maritta ), Liedgren, S. (Sigrun), Rookus, M.A. (M.), Verhoef, S. (S.), Schmidt, M.K. (Marjanka), Lange, J.L. (J.) de, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Aalfs, C.M. (Cora), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gomez Garcia, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Anna), Kennedy, M.J. (John), Barton, D.E. (David), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Brady, A.F. (Angela), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Lalloo, F. (Fiona), Taylor, J. (James), Male, A. (Alison), Berlin, C. (Cheryl), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Stormorken, A. (Astrid), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Buecher, B. (Bruno), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Uhrhammer, N. (Nancy), Bonadona, V. (Valérie), Handallou, S. (Sandrine), hardouin, A. (Agnès), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Lidereau, R. (Rosette), Demange, L. (Liliane), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Frenay, M. (Marc), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Sokolowska, J. (Johanna), Bronner, M. (Myriam), Lynch, H. (Henry), Snyder, C.L. (Carrie), Angelakos, M. (Maggie), Maskiell, J. (Judi), and Dite, G.S. (Gillian)
Abstract: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associati
Published: 2013
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61. Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk

Author: Gaudet, M.M. (Mia), Kuchenbaecker, K.B. (Karoline), Vijai, J. (Joseph), Klein, R.J. (Robert), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Dunning, A.M. (Alison), Lee, A. (Andrew), Dennis, J. (Joe), Healey, S. (Sue), Dicks, E. (Ed), Soucy, P. (Penny), Sinilnikova, O. (Olga), Pankratz, V.S. (Shane), Wang, X. (Xing), Eldridge, S. (Steve), Tessier, Y. (Yann), Vincent, D. (Daniel), Bacot, F. (Francois), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Peterlongo, P. (Paolo), Schmutzler, R.K. (Rita), Nathanson, K.L. (Katherine), Piedmonte, M. (Marion), Singer, C.F. (Christian), Thomassen, M. (Mads), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Blanco, I. (Ignacio), Greene, M.H. (Mark), Garber, J., Weitzel, J.N. (Jeffrey), Andrulis, I.L. (Irene), Goldgar, D. (David), D'Andrea, E. (Emma), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Rensburg, E.J. (Elizabeth) van, Arason, A. (Adalgeir), Rennert, G. (Gad), Ouweland, A.M.W. (Ans) van den, Hout, A.H. (Annemarie) van der, Kets, C.M. (Marleen), Aalfs, C.M. (Cora), Wijnen, J.T. (Juul), Ausems, M.G.E.M. (Margreet), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Jacobs, C. (Chris), Adlard, J.W. (Julian), Tischkowitz, M. (Marc), Porteous, M.E. (Mary), Damiola, F. (Francesca), Golmard, L. (Lisa), Barjhoux, L. (Laure), Longy, M. (Michel), Belotti, M. (Muriel), Ferrer, S.F., Mazoyer, S. (Sylvie), Spurdle, A.B. (Amanda), Manoukian, S. (Siranoush), Barile, M. (Monica), Genuardi, M. (Maurizio), Arnold, N. (Norbert), Meindl, A. (Alfons), Sutter, C. (Christian), Wapenschmidt, B. (Barbara), Domchek, S.M. (Susan), Pfeiler, G. (Georg), Friedman, E. (Eitan), Jensen, U.B., Robson, M. (Mark), Shah, S. (Sonia), Lázaro, C. (Conxi), Mai, P.L. (Phuong), Benítez, J. (Javier), Southey, M.C. (Melissa), Schmidt, M.K. (Marjanka), Fasching, P.A. (Peter), Peto, J. (Julian), Humphreys, M.K. (Manjeet), Wang, Q. (Qing), Michailidou, K. (Kyriaki), Sawyer, E.J. (Elinor), Burwinkel, B. (Barbara), Guénel, P. (Pascal), Bojesen, S.E. (Stig), Milne, R.L. (Roger), Brenner, H. (Hermann), Lochmann, M. (Magdalena), Brauch, H. (Hiltrud), Ko, Y-D. (Yon-Dschun), Baisch, C. (Christian), Fischer, H.-P., Bruening, T. (Thomas), Pesch, B. (Beate), Rabstein, S. (Sylvia), Spickenheuer, A. (Anne), Aittomäki, K. (Kristiina), Dörk, T. (Thilo), Margolin, S. (Sara), Mannermaa, A. (Arto), Lambrechts, D. (Diether), Chang-Claude, J. (Jenny), Radice, P. (Paolo), Giles, G.G. (Graham), Haiman, C.A. (Christopher), Winqvist, R. (Robert), Devillee, P. (Peter), García-Closas, M. (Montserrat), Schoof, N. (Nils), Hooning, M.J. (Maartje), Cox, A. (Angela), Pharoah, P.D.P. (Paul), Jakubowska, A. (Anna), Orr, N. (Nick), González-Neira, A. (Anna), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Hall, A.S. (Alistair), Couch, F.J. (Fergus), Simard, J. (Jacques), Altshuler, D. (David), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Offit, K. (Kenneth), Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Verhoef, S., Lange, J.L. (J.) de, Collée, J.M. (Margriet), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Devilee, P. (Peter), Cronenburg, T.C.T.E.F. van, Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Os, T.A.M. (Theo) van, Gille, J.J. (Johan), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gómez García, E.B. (Encarna), Blok, M.J. (Marinus), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Gregory, H. (Helen), Morrison, P.J. (Patrick), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), Donaldson, A. (Alan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Alexandra), Rogers, M.T. (Mark), McCann, E. (Emma), Kennedy, M.J. (John), Barton, D.E. (David), Drummond, S. (Sarah), Brewer, C. (C.), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Izatt, L. (Louise), Langman, C. (Caroline), Brady, A.F. (Angela), Dorkins, H. (Huw), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Houghton, C. (Catherine), Lalloo, F. (Fiona), Taylor, J. (James), Side, L. (Lucy), Male, A. (Alison), Berlin, C. (Cheryl), Eason, J. (Jacqueline), Collier, R. (Rebecca), Douglas, F. (Fiona), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Eeles, R. (Rosalind), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Cook, J. (Jackie), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Hodgson, S.V. (Shirley), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Eccles, D. (Diana), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Léone, M. (Mélanie), Gauthier-Villars, M. (Marion), Buecher, B. (Bruno), Houdayer, C. (Claude), Moncoutier, V. (Virginie), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Handallou, S. (Sandrine), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Sobol, H. (Hagay), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Coupier, I. (Isabelle), Pujol, P. (Pascal), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Rouleau, E. (Etienne), Lidereau, R. (Rosette), Demange, L. (Liliane), Nogues, C. (Catherine), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Frenay, M. (Marc), Vénat-Bouvet, L. (Laurence), Delnatte, C.D. (Capucine), Mortemousque, I. (Isabelle), Lynch, H. (Henry), Snyder, C.L. (Carrie), Gaudet, M.M. (Mia), Kuchenbaecker, K.B. (Karoline), Vijai, J. (Joseph), Klein, R.J. (Robert), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Dunning, A.M. (Alison), Lee, A. (Andrew), Dennis, J. (Joe), Healey, S. (Sue), Dicks, E. (Ed), Soucy, P. (Penny), Sinilnikova, O. (Olga), Pankratz, V.S. (Shane), Wang, X. (Xing), Eldridge, S. (Steve), Tessier, Y. (Yann), Vincent, D. (Daniel), Bacot, F. (Francois), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Peterlongo, P. (Paolo), Schmutzler, R.K. (Rita), Nathanson, K.L. (Katherine), Piedmonte, M. (Marion), Singer, C.F. (Christian), Thomassen, M. (Mads), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Blanco, I. (Ignacio), Greene, M.H. (Mark), Garber, J., Weitzel, J.N. (Jeffrey), Andrulis, I.L. (Irene), Goldgar, D. (David), D'Andrea, E. (Emma), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Rensburg, E.J. (Elizabeth) van, Arason, A. (Adalgeir), Rennert, G. (Gad), Ouweland, A.M.W. (Ans) van den, Hout, A.H. (Annemarie) van der, Kets, C.M. (Marleen), Aalfs, C.M. (Cora), Wijnen, J.T. (Juul), Ausems, M.G.E.M. (Margreet), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Jacobs, C. (Chris), Adlard, J.W. (Julian), Tischkowitz, M. (Marc), Porteous, M.E. (Mary), Damiola, F. (Francesca), Golmard, L. (Lisa), Barjhoux, L. (Laure), Longy, M. (Michel), Belotti, M. (Muriel), Ferrer, S.F., Mazoyer, S. (Sylvie), Spurdle, A.B. (Amanda), Manoukian, S. (Siranoush), Barile, M. (Monica), Genuardi, M. (Maurizio), Arnold, N. (Norbert), Meindl, A. (Alfons), Sutter, C. (Christian), Wapenschmidt, B. (Barbara), Domchek, S.M. (Susan), Pfeiler, G. (Georg), Friedman, E. (Eitan), Jensen, U.B., Robson, M. (Mark), Shah, S. (Sonia), Lázaro, C. (Conxi), Mai, P.L. (Phuong), Benítez, J. (Javier), Southey, M.C. (Melissa), Schmidt, M.K. (Marjanka), Fasching, P.A. (Peter), Peto, J. (Julian), Humphreys, M.K. (Manjeet), Wang, Q. (Qing), Michailidou, K. (Kyriaki), Sawyer, E.J. (Elinor), Burwinkel, B. (Barbara), Guénel, P. (Pascal), Bojesen, S.E. (Stig), Milne, R.L. (Roger), Brenner, H. (Hermann), Lochmann, M. (Magdalena), Brauch, H. (Hiltrud), Ko, Y-D. (Yon-Dschun), Baisch, C. (Christian), Fischer, H.-P., Bruening, T. (Thomas), Pesch, B. (Beate), Rabstein, S. (Sylvia), Spickenheuer, A. (Anne), Aittomäki, K. (Kristiina), Dörk, T. (Thilo), Margolin, S. (Sara), Mannermaa, A. (Arto), Lambrechts, D. (Diether), Chang-Claude, J. (Jenny), Radice, P. (Paolo), Giles, G.G. (Graham), Haiman, C.A. (Christopher), Winqvist, R. (Robert), Devillee, P. (Peter), García-Closas, M. (Montserrat), Schoof, N. (Nils), Hooning, M.J. (Maartje), Cox, A. (Angela), Pharoah, P.D.P. (Paul), Jakubowska, A. (Anna), Orr, N. (Nick), González-Neira, A. (Anna), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Hall, A.S. (Alistair), Couch, F.J. (Fergus), Simard, J. (Jacques), Altshuler, D. (David), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Offit, K. (Kenneth), Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Verhoef, S., Lange, J.L. (J.) de, Collée, J.M. (Margriet), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Devilee, P. (Peter), Cronenburg, T.C.T.E.F. van, Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Os, T.A.M. (Theo) van, Gille, J.J. (Johan), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gómez García, E.B. (Encarna), Blok, M.J. (Marinus), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Gregory, H. (Helen), Morrison, P.J. (Patrick), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), Donaldson, A. (Alan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Alexandra), Rogers, M.T. (Mark), McCann, E. (Emma), Kennedy, M.J. (John), Barton, D.E. (David), Drummond, S. (Sarah), Brewer, C. (C.), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Izatt, L. (Louise), Langman, C. (Caroline), Brady, A.F. (Angela), Dorkins, H. (Huw), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Houghton, C. (Catherine), Lalloo, F. (Fiona), Taylor, J. (James), Side, L. (Lucy), Male, A. (Alison), Berlin, C. (Cheryl), Eason, J. (Jacqueline), Collier, R. (Rebecca), Douglas, F. (Fiona), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Eeles, R. (Rosalind), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Cook, J. (Jackie), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Hodgson, S.V. (Shirley), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Eccles, D. (Diana), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Léone, M. (Mélanie), Gauthier-Villars, M. (Marion), Buecher, B. (Bruno), Houdayer, C. (Claude), Moncoutier, V. (Virginie), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Handallou, S. (Sandrine), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Sobol, H. (Hagay), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Coupier, I. (Isabelle), Pujol, P. (Pascal), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Rouleau, E. (Etienne), Lidereau, R. (Rosette), Demange, L. (Liliane), Nogues, C. (Catherine), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Frenay, M. (Marc), Vénat-Bouvet, L. (Laurence), Delnatte, C.D. (Capucine), Mortemousque, I. (Isabelle), Lynch, H. (Henry), and Snyder, C.L. (Carrie)
Published: 2013
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62. Tamoxifen and Risk of Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers

Author: Phillips, KA, Milne, RL, Rookus, MA, Daly, MB, Antoniou, AC, Peock, S, Frost, D, Easton, DF, Ellis, S, Friedlander, ML, Buys, SS, Andrieu, N, Nogues, C, Stoppa-Lyonnet, D, Bonadona, V, Pujol, P, McLachlan, SA, John, EM, Hooning, Maartje, Seynaeve, Caroline, Tollenaar, RAEM, Goldgar, DE, Terry, MB, Caldes, T, Weideman, PC, Andrulis, IL, Singer, CF, Birch, K, Simard, J, Southey, MC, Olsson, HL, Jakubowska, A, Olah, E, Gerdes, AM, Foretova, L, Hopper, JL, Phillips, KA, Milne, RL, Rookus, MA, Daly, MB, Antoniou, AC, Peock, S, Frost, D, Easton, DF, Ellis, S, Friedlander, ML, Buys, SS, Andrieu, N, Nogues, C, Stoppa-Lyonnet, D, Bonadona, V, Pujol, P, McLachlan, SA, John, EM, Hooning, Maartje, Seynaeve, Caroline, Tollenaar, RAEM, Goldgar, DE, Terry, MB, Caldes, T, Weideman, PC, Andrulis, IL, Singer, CF, Birch, K, Simard, J, Southey, MC, Olsson, HL, Jakubowska, A, Olah, E, Gerdes, AM, Foretova, L, and Hopper, JL
Abstract: Purpose To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers. Methods Analysis of pooled observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated Results Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC diagnosis. There were 520 CBCs over 20,104 person-years of observation. The adjusted HR estimates were 0.38 (95% CI, 0.27 to 0.55) and 0.33 (95% CI, 0.22 to 0.50) for BRCA1 and BRCA2 mutation carriers, respectively. After left truncating at recruitment to the cohort, adjusted HR estimates were 0.58 (95% CI, 0.29 to 1.13) and 0.48 (95% CI, 0.22 to 1.05) based on 657 BRCA1 and 426 B Conclusion This study provides evidence that tamoxifen use is associated with a reduction in CBC risk for BRCA1 and BRCA2 mutation carriers. Further follow-up of these cohorts will provide increased statistical power for future prospective analyses.
Published: 2013

63. Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

Author: Ramus, S.J., Antoniou, A.C., Kuchenbaecker, K.B., Soucy, P., Beesley, J., Chen, X., McGuffog, L., Sinilnikova, O.M., Healey, S., Barrowdale, D., Lee, A., Thomassen, M., Gerdes, A.M., Kruse, T.A., Jensen, U.B., Skytte, A.B., Caligo, M.A., Liljegren, A., Lindblom, A., Olsson, H., Kristoffersson, U., Stenmark-Askmalm, M., Melin, B., Swe, B., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Zlowocka, E., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Toloczko-Grabarek, A., Osorio, A., Benitez, J., Duran, M., Tejada, M.I., Hamann, U., Rookus, M., van Leeuwen, F.E., Aalfs, C.M., Meijers-Heijboer, H.E., Asperen, C.J. van, van Roozendaal, K.E., Hoogerbrugge-van der Linden, N., Collee, J.M., Kriege, M., van der Luijt, R.B., Hebon, ., Embrace, ., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Lalloo, F., Jacobs, C, Eeles, R., Adlard, J., Davidson, R., Eccles, D., Cole, T., Cook, J.L., Paterson, J., Douglas, F., Brewer, C., Hodgson, S., Morrison, P.J., Walker, L., Porteous, M.E., Kennedy, M.J., Pathak, H., Godwin, A.K., Stoppa-Lyonnet, D., Caux-Moncoutier, V., de Pauw, A., Gauthier-Villars, M., Mazoyer, S., Leone, M., Calender, A., Lasset, C., Bonadona, V., Hardouin, A., Berthet, P., Bignon, Y.J., Uhrhammer, N., Faivre, L., Loustalot, C., Gemo, ., Buys, S., Daly, M., Miron, A., Terry, M.B., Chung, W.K., John, E.M., Ligtenberg, M.J., et al., Ramus, S.J., Antoniou, A.C., Kuchenbaecker, K.B., Soucy, P., Beesley, J., Chen, X., McGuffog, L., Sinilnikova, O.M., Healey, S., Barrowdale, D., Lee, A., Thomassen, M., Gerdes, A.M., Kruse, T.A., Jensen, U.B., Skytte, A.B., Caligo, M.A., Liljegren, A., Lindblom, A., Olsson, H., Kristoffersson, U., Stenmark-Askmalm, M., Melin, B., Swe, B., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Jakubowska, A., Lubinski, J., Jaworska, K., Durda, K., Zlowocka, E., Gronwald, J., Huzarski, T., Byrski, T., Cybulski, C., Toloczko-Grabarek, A., Osorio, A., Benitez, J., Duran, M., Tejada, M.I., Hamann, U., Rookus, M., van Leeuwen, F.E., Aalfs, C.M., Meijers-Heijboer, H.E., Asperen, C.J. van, van Roozendaal, K.E., Hoogerbrugge-van der Linden, N., Collee, J.M., Kriege, M., van der Luijt, R.B., Hebon, ., Embrace, ., Peock, S., Frost, D., Ellis, S.D., Platte, R., Fineberg, E., Evans, D.G., Lalloo, F., Jacobs, C, Eeles, R., Adlard, J., Davidson, R., Eccles, D., Cole, T., Cook, J.L., Paterson, J., Douglas, F., Brewer, C., Hodgson, S., Morrison, P.J., Walker, L., Porteous, M.E., Kennedy, M.J., Pathak, H., Godwin, A.K., Stoppa-Lyonnet, D., Caux-Moncoutier, V., de Pauw, A., Gauthier-Villars, M., Mazoyer, S., Leone, M., Calender, A., Lasset, C., Bonadona, V., Hardouin, A., Berthet, P., Bignon, Y.J., Uhrhammer, N., Faivre, L., Loustalot, C., Gemo, ., Buys, S., Daly, M., Miron, A., Terry, M.B., Chung, W.K., John, E.M., Ligtenberg, M.J., and et al.
Abstract: Item does not contain fulltext, Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 x 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 x 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 x 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.
Published: 2012

64. Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

Author: Ramus, S.J., Kartsonaki, C., Gayther, S.A., Pharoah, P.D., Sinilnikova, O.M., Beesley, J., Chen, X., McGuffog, L., Healey, S., Couch, F.J., Wang, X., Fredericksen, Z., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Roversi, G., Barile, M., Viel, A., Allavena, A., Ottini, L., Papi, L., Gismondi, V., Capra, F., Radice, P., Greene, M.H., Mai, P.L., Andrulis, I.L., Glendon, G., Ozcelik, H., Thomassen, M., Gerdes, A.M., Kruse, T.A., Cruger, D., Jensen, U.B., Caligo, M.A., Olsson, H., Kristoffersson, U., Lindblom, A., Arver, B., Karlsson, P., Stenmark Askmalm, M., Borg, A., Neuhausen, S.L., Ding, Y.C., Nathanson, K.L., Domchek, S.M., Jakubowska, A., Lubinski, J., Huzarski, T., Byrski, T., Gronwald, J., Gorski, B., Cybulski, C., Debniak, T., Osorio, A., Duran, M., Tejada, M.I., Benitez, J., Hamann, U., Rookus, M.A., Verhoef, S., Tilanus-Linthorst, M.A., Vreeswijk, M.P., Bodmer, D., Ausems, M.G., Os, T.A. van, Asperen, C.J. van, Blok, M.J., Meijers-Heijboer, H.E., Peock, S., Cook, M., Oliver, C., Frost, D., Dunning, A.M., Evans, D.G., Eeles, R., Pichert, G., Cole, T., Hodgson, S., Brewer, C., Morrison, P.J., Porteous, M., Kennedy, M.J., Rogers, M.T., Side, L.E., Donaldson, A., Gregory, H., Godwin, A., Stoppa-Lyonnet, D., Moncoutier, V., Castera, L., Mazoyer, S., Barjhoux, L., Bonadona, V., Leroux, D., Faivre, L., Lidereau, R., Nogues, C., Bignon, Y.J., Prieur, F., Collonge-Rame, M.A., Venat-Bouvet, L., Ligtenberg, M.J.L., et al., Ramus, S.J., Kartsonaki, C., Gayther, S.A., Pharoah, P.D., Sinilnikova, O.M., Beesley, J., Chen, X., McGuffog, L., Healey, S., Couch, F.J., Wang, X., Fredericksen, Z., Peterlongo, P., Manoukian, S., Peissel, B., Zaffaroni, D., Roversi, G., Barile, M., Viel, A., Allavena, A., Ottini, L., Papi, L., Gismondi, V., Capra, F., Radice, P., Greene, M.H., Mai, P.L., Andrulis, I.L., Glendon, G., Ozcelik, H., Thomassen, M., Gerdes, A.M., Kruse, T.A., Cruger, D., Jensen, U.B., Caligo, M.A., Olsson, H., Kristoffersson, U., Lindblom, A., Arver, B., Karlsson, P., Stenmark Askmalm, M., Borg, A., Neuhausen, S.L., Ding, Y.C., Nathanson, K.L., Domchek, S.M., Jakubowska, A., Lubinski, J., Huzarski, T., Byrski, T., Gronwald, J., Gorski, B., Cybulski, C., Debniak, T., Osorio, A., Duran, M., Tejada, M.I., Benitez, J., Hamann, U., Rookus, M.A., Verhoef, S., Tilanus-Linthorst, M.A., Vreeswijk, M.P., Bodmer, D., Ausems, M.G., Os, T.A. van, Asperen, C.J. van, Blok, M.J., Meijers-Heijboer, H.E., Peock, S., Cook, M., Oliver, C., Frost, D., Dunning, A.M., Evans, D.G., Eeles, R., Pichert, G., Cole, T., Hodgson, S., Brewer, C., Morrison, P.J., Porteous, M., Kennedy, M.J., Rogers, M.T., Side, L.E., Donaldson, A., Gregory, H., Godwin, A., Stoppa-Lyonnet, D., Moncoutier, V., Castera, L., Mazoyer, S., Barjhoux, L., Bonadona, V., Leroux, D., Faivre, L., Lidereau, R., Nogues, C., Bignon, Y.J., Prieur, F., Collonge-Rame, M.A., Venat-Bouvet, L., Ligtenberg, M.J.L., and et al.
Abstract: Item does not contain fulltext, BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2. METHODS: We genotyped rs3814113 in 10,029 BRCA1 mutation carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided. RESULTS: The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 x 10(-9)) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 x 10(-4)). This SNP was not associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers. BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to have an ovarian cancer risk to age 80 years of 48%, and those with the CC genotype were predicted to have a risk of 33%. CONCLUSION: Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a BRCA1 or BRCA2 mutation.
Published: 2011

65. Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

Author: Ramus, S.J. (Susan), Kartsonaki, C. (Christiana), Gayther, S.A. (Simon), Pharoah, P.D.P. (Paul), Sinilnikova, O. (Olga), Beesley, J. (Jonathan), Chenevix-Trench, G. (Georgia), McGuffog, L. (Lesley), Healey, S. (Sue), Couch, F.J. (Fergus), Wang, X. (Xing), Fredericksen, Z. (Zachary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Roversi, G. (Gaia), Barile, M. (Monica), Viel, A. (Alessandra), Allavena, A. (Anna), Ottini, L. (Laura), Papi, L. (Laura), Gismondi, V. (Viviana), Capra, F. (Fabio), Radice, P. (Paolo), Greene, M.H. (Mark), Mai, P.L. (Phuong), Andrulis, I.L. (Irene), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Kruse, T.A. (Torben), Cruger, D. (Dorthe), Jensen, U.B., Caligo, M.A. (Maria), Olsson, H. (Hkan), Kristoffersson, U. (Ulf), Lindblom, A. (Annika), Arver, B. (Brita Wasteson), Karlsson, P. (Per), Stenmark-Askmalm, M. (M.), Borg, Å. (Åke), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Gronwald, J. (Jacek), Górski, B. (Bohdan), Cybulski, C. (Cezary), Dbniak, T. (Tadeusz), Osorio, A. (Ana), Durán, M. (Mercedes), Tejada, M.-I., Benitez, J. (Javier), Hamann, U. (Ute), Rookus, M.A. (Matti), Verhoef, S., Tilanus-Linthorst, M.M.A. (Madeleine), Vreeswijk, M.P. (Maaike), Bodmer, D. (Danielle), Ausems, M.G.E.M. (Margreet), Os, T.A.M. (Theo) van, Blok, M.J. (Marinus), Meijers-Heijboer, H. (Hanne), Peock, S. (Susan), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Dunning, A.M. (Alison), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Pichert, G. (Gabriella), Cole, T.J. (Trevor), Hodgson, S.V. (Shirley), Brewer, C. (Carole), Morrison, P.J. (Patrick), Porteous, M.E. (Mary), Kennedy, M.J. (John), Rogers, M.T. (Mark), Side, L. (Lucy), Donaldson, A. (Alan), Gregory, H. (Helen), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Moncoutier, V. (Virginie), Castera, L. (Laurent), Mazoyer, S. (Sylvie), Barjhoux, L. (Laure), Bonadona, V. (Valérie), Leroux, D. (Dominique), Faivre, L. (Laurence), Lidereau, R. (Rosette), Nogues, C. (Catherine), Bignon, Y.-J. (Yves-Jean), Prieur, F. (Fabienne), Collonge-Rame, M.-A., Vénat-Bouvet, L. (Laurence), Fert-Ferrer, S. (Sandra), Miron, A. (Alexander), Buys, S.S. (Saundra), Hopper, J. (John), Daly, M.J. (Mark), John, E.M. (Esther), Terry, M-B. (Mary-beth), Goldgar, D. (David), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Agnarsson, B.A. (Bjarni), Offit, K. (Kenneth), Kircchoff, T. (Tomas), Vijai, J. (Joseph), Dutra-Clarke, A. (Ana), Przybylo, J.A. (Jennifer), Montagna, M. (Marco), Casella, C. (Cinzia), Imyanitov, E.N. (Evgeny), Janavicius, R. (Ramunas), Blanco, I. (Ignacio), Lázaro, C. (Conxi), Moysich, K.B. (Kirsten), Karlan, B.Y. (Beth), Gross, J. (Jenny), Beattie, M.S. (Mary), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Meindl, A. (Alfons), Ruehl, I. (Ina), Fiebig, B. (Britta), Sutter, C. (Christian), Arnold, N. (Norbert), Deissler, H. (Helmut), Varon-Mateeva, R. (Raymonda), Kast, K. (Karin), Niederacher, D. (Dieter), Gadzicki, D. (Dorothea), Ejlertsen, B. (Bent), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Simard, J. (Jacques), Soucy, P. (Penny), Spurdle, A.B. (Amanda), Holland, H. (Helene), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), Asperen, C.J. (Christi) van, Ramus, S.J. (Susan), Kartsonaki, C. (Christiana), Gayther, S.A. (Simon), Pharoah, P.D.P. (Paul), Sinilnikova, O. (Olga), Beesley, J. (Jonathan), Chenevix-Trench, G. (Georgia), McGuffog, L. (Lesley), Healey, S. (Sue), Couch, F.J. (Fergus), Wang, X. (Xing), Fredericksen, Z. (Zachary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Roversi, G. (Gaia), Barile, M. (Monica), Viel, A. (Alessandra), Allavena, A. (Anna), Ottini, L. (Laura), Papi, L. (Laura), Gismondi, V. (Viviana), Capra, F. (Fabio), Radice, P. (Paolo), Greene, M.H. (Mark), Mai, P.L. (Phuong), Andrulis, I.L. (Irene), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Kruse, T.A. (Torben), Cruger, D. (Dorthe), Jensen, U.B., Caligo, M.A. (Maria), Olsson, H. (Hkan), Kristoffersson, U. (Ulf), Lindblom, A. (Annika), Arver, B. (Brita Wasteson), Karlsson, P. (Per), Stenmark-Askmalm, M. (M.), Borg, Å. (Åke), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Gronwald, J. (Jacek), Górski, B. (Bohdan), Cybulski, C. (Cezary), Dbniak, T. (Tadeusz), Osorio, A. (Ana), Durán, M. (Mercedes), Tejada, M.-I., Benitez, J. (Javier), Hamann, U. (Ute), Rookus, M.A. (Matti), Verhoef, S., Tilanus-Linthorst, M.M.A. (Madeleine), Vreeswijk, M.P. (Maaike), Bodmer, D. (Danielle), Ausems, M.G.E.M. (Margreet), Os, T.A.M. (Theo) van, Blok, M.J. (Marinus), Meijers-Heijboer, H. (Hanne), Peock, S. (Susan), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Dunning, A.M. (Alison), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Pichert, G. (Gabriella), Cole, T.J. (Trevor), Hodgson, S.V. (Shirley), Brewer, C. (Carole), Morrison, P.J. (Patrick), Porteous, M.E. (Mary), Kennedy, M.J. (John), Rogers, M.T. (Mark), Side, L. (Lucy), Donaldson, A. (Alan), Gregory, H. (Helen), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Moncoutier, V. (Virginie), Castera, L. (Laurent), Mazoyer, S. (Sylvie), Barjhoux, L. (Laure), Bonadona, V. (Valérie), Leroux, D. (Dominique), Faivre, L. (Laurence), Lidereau, R. (Rosette), Nogues, C. (Catherine), Bignon, Y.-J. (Yves-Jean), Prieur, F. (Fabienne), Collonge-Rame, M.-A., Vénat-Bouvet, L. (Laurence), Fert-Ferrer, S. (Sandra), Miron, A. (Alexander), Buys, S.S. (Saundra), Hopper, J. (John), Daly, M.J. (Mark), John, E.M. (Esther), Terry, M-B. (Mary-beth), Goldgar, D. (David), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Agnarsson, B.A. (Bjarni), Offit, K. (Kenneth), Kircchoff, T. (Tomas), Vijai, J. (Joseph), Dutra-Clarke, A. (Ana), Przybylo, J.A. (Jennifer), Montagna, M. (Marco), Casella, C. (Cinzia), Imyanitov, E.N. (Evgeny), Janavicius, R. (Ramunas), Blanco, I. (Ignacio), Lázaro, C. (Conxi), Moysich, K.B. (Kirsten), Karlan, B.Y. (Beth), Gross, J. (Jenny), Beattie, M.S. (Mary), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Meindl, A. (Alfons), Ruehl, I. (Ina), Fiebig, B. (Britta), Sutter, C. (Christian), Arnold, N. (Norbert), Deissler, H. (Helmut), Varon-Mateeva, R. (Raymonda), Kast, K. (Karin), Niederacher, D. (Dieter), Gadzicki, D. (Dorothea), Ejlertsen, B. (Bent), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Simard, J. (Jacques), Soucy, P. (Penny), Spurdle, A.B. (Amanda), Holland, H. (Helene), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), and Asperen, C.J. (Christi) van
Abstract: Background Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2. Method sWe genotyped rs3814113 in 10029 BRCA1 mutation carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided. Results The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 × 10-9) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 × 10-4). This SNP was not associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers. BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to have an ovarian cancer risk to age 80 years of 48%, and those with the CC genotype were predicted to have a risk of 33%. Conclusion Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a BRCA1 or BRCA2 mutation.
Published: 2011
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66. Molecular study of the perforin gene in familial hematological malignancies

Author: El Abed, R, Bourdon, V, Voskoboinik, I, Omri, H, Ben Youssef, Y, Laatiri, MA, Huiart, L, Eisinger, F, Rabayrol, L, Frenay, M, Gesta, P, Demange, L, Dreyfus, H, Bonadona, V, Dugast, C, Zattara, H, Faivre, L, Zaier, M, Jemni, SY, Noguchi, T, Sobol, H, Soua, Z, El Abed, R, Bourdon, V, Voskoboinik, I, Omri, H, Ben Youssef, Y, Laatiri, MA, Huiart, L, Eisinger, F, Rabayrol, L, Frenay, M, Gesta, P, Demange, L, Dreyfus, H, Bonadona, V, Dugast, C, Zattara, H, Faivre, L, Zaier, M, Jemni, SY, Noguchi, T, Sobol, H, and Soua, Z
Abstract: Perforin gene (PRF1) mutations have been identified in some patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH) and in patients with lymphoma. The aim of the present study was to determine whether patients with a familial aggregation of hematological malignancies harbor germline perforin gene mutations. For this purpose, 81 unrelated families from Tunisia and France with aggregated hematological malignancies were investigated. The variants detected in the PRF1 coding region amounted to 3.7% (3/81). Two of the three variants identified were previously described: the p.Ala91Val pathogenic mutation and the p.Asn252Ser polymorphism. A new p.Ala 211Val missense substitution was identified in two related Tunisian patients. In order to assess the pathogenicity of this new variation, bioinformatic tools were used to predict its effects on the perforin protein structure and at the mRNA level. The segregation of the mutant allele was studied in the family of interest and a control population was screened. The fact that this variant was not found to occur in 200 control chromosomes suggests that it may be pathogenic. However, overexpression of mutated PRF1 in rat basophilic leukemia cells did not affect the lytic function of perforin differently from the wild type protein.
Published: 2011

67. Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

Author: Ramus, S, Kartsonaki, C, Gayther, S, Pharoah, P, Sinilnikova, O, Beesley, J, Chen, X, Mcguffog, L, Healey, S, Couch, F, Wang, X, Fredericksen, Z, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Barile, M, Viel, A, Allavena, A, Ottini, L, Papi, L, Gismondi, V, Capra, F, Radice, P, Greene, M, Mai, P, Andrulis, I, Glendon, G, Ozcelik, H, Thomassen, M, Gerdes, A, Kruse, T, Cruger, D, Jensen, U, Caligo, M, Olsson, H, Kristoffersson, U, Lindblom, A, Arver, B, Karlsson, P, Stenmark Askmalm, M, Borg, A, Neuhausen, S, Ding, Y, Nathanson, K, Domchek, S, Jakubowska, A, Lubiński, J, Huzarski, T, Byrski, T, Gronwald, J, Górski, B, Cybulski, C, Dębniak, T, Osorio, A, Durán, M, Tejada, M, Benítez, J, Hamann, U, Rookus, M, Verhoef, S, Tilanus Linthorst, M, Vreeswijk, M, Bodmer, D, Ausems, M, van Os, T, Asperen, C, Blok, M, Meijers Heijboer, H, Peock, S, Cook, M, Oliver, C, Frost, D, Dunning, A, Evans, D, Eeles, R, Pichert, G, Cole, T, Hodgson, S, Brewer, C, Morrison, P, Porteous, M, Kennedy, M, Rogers, M, Side, L, Donaldson, A, Gregory, H, Godwin, A, Stoppa Lyonnet, D, Moncoutier, V, Castera, L, Mazoyer, S, Barjhoux, L, Bonadona, V, Leroux, D, Faivre, L, Lidereau, R, Nogues, C, Bignon, Y, Prieur, F, Collonge Rame, M, Venat Bouvet, L, Fert Ferrer, S, Miron, A, Buys, S, Hopper, J, Daly, M, John, E, Terry, M, Goldgar, D, Hansen, T, Jønson, L, Ejlertsen, B, Agnarsson, B, Offit, K, Kirchhoff, T, Vijai, J, Dutra Clarke, A, Przybylo, J, Montagna, M, Casella, C, Imyanitov, E, Janavicius, R, Blanco, I, Lázaro, C, Moysich, K, Karlan, B, Gross, J, Beattie, M, Schmutzler, R, Wappenschmidt, B, Meindl, A, Ruehl, I, Fiebig, B, Sutter, C, Arnold, N, Deissler, H, Varon Mateeva, R, Kast, K, Niederacher, D, Gadzicki, D, Caldes, T, de la Hoya, M, Nevanlinna, H, Aittomäki, K, Simard, J, Soucy, P, Spurdle, A, Holland, H, Chenevix Trench, G, Easton, D, Antoniou, A, Ramus, SJ, Gayther, SA, Pharoah, PDP, Sinilnikova, OM, McGuffog, L, Couch, FJ, Greene, MH, Mai, PL, Andrulis, IL, Kruse, TA, Jensen, UB, Caligo, MA, Neuhausen, SL, Ding, YC, Nathanson, KL, Domchek, SM, Rookus, MA, Tilanus Linthorst, MA, Vreeswijk, MP, Ausems, MGEM, van Os, TA, Asperen, CJ, Blok, MJ, Meijers Heijboer, HEJ, Dunning, AM, Evans, DG, Morrison, PJ, Kennedy, MJ, Rogers, MT, Side, LE, Buys, SS, Hopper, JL, Daly, MB, John, EM, Terry, MB, Hansen, TvO, Agnarsson, BA, Dutra Clarke, AVC, Przybylo, JA, Imyanitov, EN, Moysich, KB, Karlan, BY, Beattie, MS, Spurdle, AB, Easton, DF, Antoniou, AC, ROVERSI, GAIA, Ramus, S, Kartsonaki, C, Gayther, S, Pharoah, P, Sinilnikova, O, Beesley, J, Chen, X, Mcguffog, L, Healey, S, Couch, F, Wang, X, Fredericksen, Z, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Barile, M, Viel, A, Allavena, A, Ottini, L, Papi, L, Gismondi, V, Capra, F, Radice, P, Greene, M, Mai, P, Andrulis, I, Glendon, G, Ozcelik, H, Thomassen, M, Gerdes, A, Kruse, T, Cruger, D, Jensen, U, Caligo, M, Olsson, H, Kristoffersson, U, Lindblom, A, Arver, B, Karlsson, P, Stenmark Askmalm, M, Borg, A, Neuhausen, S, Ding, Y, Nathanson, K, Domchek, S, Jakubowska, A, Lubiński, J, Huzarski, T, Byrski, T, Gronwald, J, Górski, B, Cybulski, C, Dębniak, T, Osorio, A, Durán, M, Tejada, M, Benítez, J, Hamann, U, Rookus, M, Verhoef, S, Tilanus Linthorst, M, Vreeswijk, M, Bodmer, D, Ausems, M, van Os, T, Asperen, C, Blok, M, Meijers Heijboer, H, Peock, S, Cook, M, Oliver, C, Frost, D, Dunning, A, Evans, D, Eeles, R, Pichert, G, Cole, T, Hodgson, S, Brewer, C, Morrison, P, Porteous, M, Kennedy, M, Rogers, M, Side, L, Donaldson, A, Gregory, H, Godwin, A, Stoppa Lyonnet, D, Moncoutier, V, Castera, L, Mazoyer, S, Barjhoux, L, Bonadona, V, Leroux, D, Faivre, L, Lidereau, R, Nogues, C, Bignon, Y, Prieur, F, Collonge Rame, M, Venat Bouvet, L, Fert Ferrer, S, Miron, A, Buys, S, Hopper, J, Daly, M, John, E, Terry, M, Goldgar, D, Hansen, T, Jønson, L, Ejlertsen, B, Agnarsson, B, Offit, K, Kirchhoff, T, Vijai, J, Dutra Clarke, A, Przybylo, J, Montagna, M, Casella, C, Imyanitov, E, Janavicius, R, Blanco, I, Lázaro, C, Moysich, K, Karlan, B, Gross, J, Beattie, M, Schmutzler, R, Wappenschmidt, B, Meindl, A, Ruehl, I, Fiebig, B, Sutter, C, Arnold, N, Deissler, H, Varon Mateeva, R, Kast, K, Niederacher, D, Gadzicki, D, Caldes, T, de la Hoya, M, Nevanlinna, H, Aittomäki, K, Simard, J, Soucy, P, Spurdle, A, Holland, H, Chenevix Trench, G, Easton, D, Antoniou, A, Ramus, SJ, Gayther, SA, Pharoah, PDP, Sinilnikova, OM, McGuffog, L, Couch, FJ, Greene, MH, Mai, PL, Andrulis, IL, Kruse, TA, Jensen, UB, Caligo, MA, Neuhausen, SL, Ding, YC, Nathanson, KL, Domchek, SM, Rookus, MA, Tilanus Linthorst, MA, Vreeswijk, MP, Ausems, MGEM, van Os, TA, Asperen, CJ, Blok, MJ, Meijers Heijboer, HEJ, Dunning, AM, Evans, DG, Morrison, PJ, Kennedy, MJ, Rogers, MT, Side, LE, Buys, SS, Hopper, JL, Daly, MB, John, EM, Terry, MB, Hansen, TvO, Agnarsson, BA, Dutra Clarke, AVC, Przybylo, JA, Imyanitov, EN, Moysich, KB, Karlan, BY, Beattie, MS, Spurdle, AB, Easton, DF, Antoniou, AC, and ROVERSI, GAIA
Abstract: Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2.
Published: 2011

68. Common breast cancer susceptibility alleles and the risk of breast cancer for BRCA1 and BRCA2 mutation carriers: Implications for risk prediction

Author: Antoniou, A.C. (Antonis), Beesley, J. (Jonathan), McGuffog, L. (Lesley), Sinilnikova, O. (Olga), Healey, S. (Sue), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Rebbeck, R. (Timothy), Weitzel, J.N. (Jeffrey), Lynch, H. (Henry), Isaacs, C. (Claudine), Ganz, P.A. (Patricia), Tomlinson, G. (Gail), Olopade, O.I. (Olofunmilayo), Couch, F.J. (Fergus), Wang, X. (Xing), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Radice, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Barile, M. (Monica), Viel, A. (Alessandra), Allavena, A. (Anna), Dall'Olio, V. (Valentina), Peterlongo, P. (Paolo), Szabo, C. (Csilla), Zikan, M. (Michal), Claes, K. (Kathleen), Poppe, B. (Bruce), Foretova, L. (Lenka), Mai, P.L. (Phuong), Greene, M.H. (Mark), Rennert, G. (Gad), Lejbkowicz, F. (Flavio), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Andrulis, I.L. (Irene), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Sunde, L. (Lone), Cruger, D. (Dorthe), Jensen, U.B., Caligo, M.A. (Maria), Friedman, E. (Eitan), Kaufman, B. (Bella), Laitman, Y. (Yael), Milgrom, R. (Roni), Dubrovsky, M. (Maya), Cohen, S. (Shimrit), Borg, Å. (Åke), Jernström, H. (H.), Lindblom, A. (Annika), Rantala, J. (Johanna), Stenmark-Askmalm, M. (M.), Melin, B. (Beatrice), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Huzarski, T. (Tomasz), Osorio, A. (Ana), Lasa, A. (Adriana), Durán, M. (Mercedes), Tejada, M.I., Godino, J. (Javier), Benitez, J. (Javier), Hamann, U. (Ute), Kriege, M. (Mieke), Hoogerbrugge, N. (Nicoline), Luijt, R.B. (Rob) van der, Asperen, C.J. (Christi) van, Devilee, P. (Peter), Meijers-Heijboer, E.J. (Hanne), Blok, M.J. (Marinus), Aalfs, C.M. (Cora), Hogervorst, F.B.L. (Frans), Rookus, M.A. (Matti), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Conroy, D. (Don), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Pichert, G. (Gabriella), Davidson, R. (Rosemarie), Cole, T.J. (Trevor), Paterson, J. (Joan), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Porteous, M.E. (Mary), Walker, L.J. (Lisa), Kennedy, M.J. (John), Dorkins, H. (Huw), Peock, S. (Susan), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Pauw, A. (Antoine) de, Mazoyer, S. (Sylvie), Bonadona, V. (Valérie), Lasset, C. (Christine), Dreyfus, H. (Hélène), Leroux, D. (Dominique), hardouin, A. (Agnès), Berthet, P. (Pascaline), Faivre, L. (Laurence), Loustalot, C. (Catherine), Noguchi, T. (Tetsuro), Sobol, H. (Hagay), Rouleau, E. (Etienne), Nogues, C. (Catherine), Frenay, M. (Marc), Vénat-Bouvet, L. (Laurence), Hopper, J. (John), Daly, M.J. (Mark), Terry, M-B. (Mary-beth), John, E.M. (Esther), Buys, S.S. (Saundra), Yassin, Y. (Yosuf), Miron, A. (Alexander), Goldgar, D. (David), Singer, C.F. (Christian), Dressler, C. (Catherina), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Hansen, T.V.O. (Thomas), Jnson, L. (Lars), Agnarsson, B.A. (Bjarni), Kircchoff, T. (Tomas), Offit, K. (Kenneth), Devlin, V. (Vincent), Dutra-Clarke, A. (Ana), Piedmonte, M. (Marion), Rodriguez, G.C. (Gustavo), Wakeley, K. (Katie), Boggess, J.F. (John), Basil, J. (Jack), Schwartz, P.E. (Peter), Blank, S.V. (Stephanie), Toland, A.E. (Amanda), Montagna, M. (Marco), Casella, C. (Cinzia), Imyanitov, E.N. (Evgeny), Tihomirova, L. (Laima), Blanco, I. (Ignacio), Lázaro, C. (Conxi), Ramus, S.J. (Susan), Sucheston, L. (Lara), Karlan, B.Y. (Beth), Gross, J. (Jenny), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Lochmann, M. (Magdalena), Arnold, N. (Norbert), Heidemann, S. (Simone), Varon-Mateeva, R. (Raymonda), Niederacher, D. (Dieter), Sutter, C. (Christian), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Schönbuchner, I. (Ines), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Aittomäki, K. (Kristiina), Nevanlinna, H. (Heli), Simard, J. (Jacques), Spurdle, A.B. (Amanda), Holland, H. (Helene), Chenevix-Trench, G. (Georgia), Platte, R. (Radka), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), Beesley, J. (Jonathan), McGuffog, L. (Lesley), Sinilnikova, O. (Olga), Healey, S. (Sue), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Rebbeck, R. (Timothy), Weitzel, J.N. (Jeffrey), Lynch, H. (Henry), Isaacs, C. (Claudine), Ganz, P.A. (Patricia), Tomlinson, G. (Gail), Olopade, O.I. (Olofunmilayo), Couch, F.J. (Fergus), Wang, X. (Xing), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Radice, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Barile, M. (Monica), Viel, A. (Alessandra), Allavena, A. (Anna), Dall'Olio, V. (Valentina), Peterlongo, P. (Paolo), Szabo, C. (Csilla), Zikan, M. (Michal), Claes, K. (Kathleen), Poppe, B. (Bruce), Foretova, L. (Lenka), Mai, P.L. (Phuong), Greene, M.H. (Mark), Rennert, G. (Gad), Lejbkowicz, F. (Flavio), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Andrulis, I.L. (Irene), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Sunde, L. (Lone), Cruger, D. (Dorthe), Jensen, U.B., Caligo, M.A. (Maria), Friedman, E. (Eitan), Kaufman, B. (Bella), Laitman, Y. (Yael), Milgrom, R. (Roni), Dubrovsky, M. (Maya), Cohen, S. (Shimrit), Borg, Å. (Åke), Jernström, H. (H.), Lindblom, A. (Annika), Rantala, J. (Johanna), Stenmark-Askmalm, M. (M.), Melin, B. (Beatrice), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Huzarski, T. (Tomasz), Osorio, A. (Ana), Lasa, A. (Adriana), Durán, M. (Mercedes), Tejada, M.I., Godino, J. (Javier), Benitez, J. (Javier), Hamann, U. (Ute), Kriege, M. (Mieke), Hoogerbrugge, N. (Nicoline), Luijt, R.B. (Rob) van der, Asperen, C.J. (Christi) van, Devilee, P. (Peter), Meijers-Heijboer, E.J. (Hanne), Blok, M.J. (Marinus), Aalfs, C.M. (Cora), Hogervorst, F.B.L. (Frans), Rookus, M.A. (Matti), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Conroy, D. (Don), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Pichert, G. (Gabriella), Davidson, R. (Rosemarie), Cole, T.J. (Trevor), Paterson, J. (Joan), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Porteous, M.E. (Mary), Walker, L.J. (Lisa), Kennedy, M.J. (John), Dorkins, H. (Huw), Peock, S. (Susan), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Pauw, A. (Antoine) de, Mazoyer, S. (Sylvie), Bonadona, V. (Valérie), Lasset, C. (Christine), Dreyfus, H. (Hélène), Leroux, D. (Dominique), hardouin, A. (Agnès), Berthet, P. (Pascaline), Faivre, L. (Laurence), Loustalot, C. (Catherine), Noguchi, T. (Tetsuro), Sobol, H. (Hagay), Rouleau, E. (Etienne), Nogues, C. (Catherine), Frenay, M. (Marc), Vénat-Bouvet, L. (Laurence), Hopper, J. (John), Daly, M.J. (Mark), Terry, M-B. (Mary-beth), John, E.M. (Esther), Buys, S.S. (Saundra), Yassin, Y. (Yosuf), Miron, A. (Alexander), Goldgar, D. (David), Singer, C.F. (Christian), Dressler, C. (Catherina), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Hansen, T.V.O. (Thomas), Jnson, L. (Lars), Agnarsson, B.A. (Bjarni), Kircchoff, T. (Tomas), Offit, K. (Kenneth), Devlin, V. (Vincent), Dutra-Clarke, A. (Ana), Piedmonte, M. (Marion), Rodriguez, G.C. (Gustavo), Wakeley, K. (Katie), Boggess, J.F. (John), Basil, J. (Jack), Schwartz, P.E. (Peter), Blank, S.V. (Stephanie), Toland, A.E. (Amanda), Montagna, M. (Marco), Casella, C. (Cinzia), Imyanitov, E.N. (Evgeny), Tihomirova, L. (Laima), Blanco, I. (Ignacio), Lázaro, C. (Conxi), Ramus, S.J. (Susan), Sucheston, L. (Lara), Karlan, B.Y. (Beth), Gross, J. (Jenny), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Lochmann, M. (Magdalena), Arnold, N. (Norbert), Heidemann, S. (Simone), Varon-Mateeva, R. (Raymonda), Niederacher, D. (Dieter), Sutter, C. (Christian), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Schönbuchner, I. (Ines), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Aittomäki, K. (Kristiina), Nevanlinna, H. (Heli), Simard, J. (Jacques), Spurdle, A.B. (Amanda), Holland, H. (Helene), Chenevix-Trench, G. (Georgia), Platte, R. (Radka), and Easton, D.F. (Douglas)
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.
Published: 2010
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69. Étude GENESIS : trois ans d’inclusion en France

Author: Eon-Marchais, S., primary, Marcou, M., additional, Toulemonde, L., additional, Dondon, M.-G., additional, Beauvallet, J., additional, Cavaciuti, E., additional, Andrieu, N., additional, Barjhoux, L., additional, Verny, C., additional, Sinilnikova, O., additional, Bonadona, V., additional, Sobol, H., additional, Noguès, C., additional, Caron, O., additional, Berthet, P., additional, Bonaïti, C., additional, Babron, M.-C., additional, and Stoppa-Lyonnet, D., additional
Published: 2011
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70. Évaluation du dépistage par IRM, mammographie et échographie chez les femmes à risque héréditaire de cancer du sein. Expérience du CLCC Léon-Bérard – Lyon

Author: Haesebaert, J., primary, Guérin, N., additional, Peix, M., additional, Bonadona, V., additional, Pleynet, E., additional, and Lasset, C., additional
Published: 2010
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71. Estimation des risques tumoraux dans le syndrome de Lynch : résultats de l’étude française ERISCAM

Author: Bonadona, V., primary, Bonaïti, B., additional, Yhuel, E., additional, Lasset, C., additional, and Bonaïti-Pellié, C., additional
Published: 2010
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72. Depistage du cancer du sein des femmes porteuses de mutation BRCA1/2 par IRM, mammographie, echographie

Author: Guérin, N., primary, Bonadona, V., additional, Peix, M., additional, Haesebaert, J., additional, Pleynet, E., additional, and Lasset, C., additional
Published: 2009
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73. Oncogénétique: estimation des besoins de la population en France pour les dix ans à venir

Author: Bonaïti-Pellié, C., additional, Andrieu, N., additional, Arveux, P., additional, Bonadona, V., additional, Buecher, B., additional, Delpech, M., additional, Jolly, D., additional, Julian-Reynier, C., additional, Luporsi, E., additional, Noguès, C., additional, Nowak, F., additional, Olschwang, S., additional, Orsi, F., additional, Pujol, P., additional, Saurin, J.-C., additional, Sinilnikova, O., additional, Stoppa-Lyonnet, D., additional, and Thépot, F., additional
Published: 2009
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74. Estimation du risque de cancer du sein dans une cohorte prospective de femmes porteuses d’une mutation sur les gènes BRCA : cohorte nationale GENEPSO

Author: Mouret-Fourme, E., primary, Andrieu, N., additional, Chompret, A., additional, Caron, O., additional, Gauthier-Villars, M., additional, Stoppa-Lyonnet, D., additional, Fricker, J.P., additional, Lasset, C., additional, Bonadona, V., additional, Berthet, P., additional, Faivre, L., additional, Luporsi, E., additional, Frénay, M., additional, Gladieff, L., additional, Guimbaud, R., additional, Gesta, P., additional, Sobol, H., additional, Huiart, L., additional, Eisinger, F., additional, Longy, M., additional, Dugast, C., additional, Colas, C., additional, Coupier, I., additional, Pujol, P., additional, Lortholary, A., additional, Vennin, P., additional, Adenis, C., additional, Nguyen, T. Dat, additional, Delnatte, C., additional, Chevrier, A., additional, Rossi, A., additional, Limacher, J.M., additional, Bignon, Y.J., additional, Demange, L., additional, Dreyfus, H., additional, Cohen-Haguenauer, O., additional, Venat-Bouvet, L., additional, Zattara-Cannoni, H., additional, Bonaïti, C., additional, and Noguès, C., additional
Published: 2009
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75. Prédispositions héréditaires au cancer du sein. Évaluation de l’information du patient sur le résultat négatif des recherches génétiques initiales

Author: Woerlé Boissy, J., primary, Charavel, M., additional, Lasset, C., additional, and Bonadona, V., additional
Published: 2008
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76. Effet du recrutement par les critères d’Amsterdam sur le risque de cancer colorectal dans les familles HNPCC sans mutation MMR identifiée

Author: Drouet, Y., primary, Bonadona, V., additional, and Lasset, C., additional
Published: 2008
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77. Prognosis of early-onset breast cancer based on BRCA1/2 mutation status in a French population-based cohort

Author: Bonadona, V., primary, Voirin, N., additional, Sinilnikova, O., additional, Mignotte, H., additional, Bremond, A., additional, Mathevet, P., additional, Romestaing, P., additional, Raudrant, D., additional, Lenoir, G., additional, and Lasset, C., additional
Published: 2006
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78. Oncogenetics and psycho-oncology: a recommended collaboration

Author: Saltel, P., primary and Bonadona, V., additional
Published: 2005
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79. E1-1 Estimation des risques associés à une mutation des gènes MLH1 ou MSH2 dans le syndrome de prédisposition héréditaire au cancer du côlon non polyposique

Author: Bonadona, V., primary, Carayol, J., additional, Lasset, C., additional, and Bonaïti-Pellie, C., additional
Published: 2004
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80. P17-7 Impact d’un livret d’information sur les connaissances, la satisfaction et la décision de demander un test génétique

Author: Mancini, J., primary, Nogues, C., additional, Chompret, A., additional, Cypowyj, C., additional, Fricker, J.P., additional, Bonadona, V., additional, Lortholary, A., additional, N’Guyen, T.D., additional, Sobol, H., additional, Stoppa-Lyonnet, D., additional, Vennin, P., additional, and Julian-Reynier, C., additional
Published: 2004
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81. P2-3 Analyse des facteurs histologiques prédictifs d’une mutation germinale de BRCA1/2 dans le cancer du sein précoce, à partir d’une étude en population

Author: Bonadona, V., primary, Moser, S., additional, Sinilnikova, O.M., additional, Bremond, A., additional, Mathevet, P., additional, Mignotte, H., additional, Martin, A., additional, Bobin, J.Y., additional, Romestaing, P., additional, Raudrant, D., additional, Rudigoz, R.C., additional, Chopin, S., additional, Lenoir, G.M., additional, and Lasset, C., additional
Published: 2004
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82. P2-10 Pronostic des cancers de l’endomètre associés à la prise de tamoxifène en traitement d’un cancer du sein. Analyse d’une série française

Author: Lasset, C., primary, Bonadona, V., additional, Mignotte, H., additional, Bailly, C., additional, Treilleux, I., additional, Becette, V., additional, Anjou, J., additional, Bremond, A., additional, and Chauvin, F., additional
Published: 2004
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83. Tamoxifen therapy for breast cancer and its relation to the prognosis and histopathology in subsequent endometrial cancer

Author: Lasset, C., primary, Bonadona, V., additional, Mignotte, H., additional, Bailly, C., additional, Treilleux, I., additional, Becette, V., additional, Anjou, J., additional, Bremond, A., additional, and Chauvin, F., additional
Published: 2004
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84. Re: Pretest Prediction of BRCA1 or BRCA2 Mutation by Risk Counselors and the Computer Model BRCAPRO

Author: Bonadona, V., primary
Published: 2002
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85. IV.4 Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case—Control study

Author: Mignotte, H., primary, Lasset, C., additional, and Bonadona, V., additional
Published: 1998
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86. Endometrial carcinoma (EC) in women with breast cancer (BC)

Author: Mignotle, H., primary, Lesur, A., additional, Luporsi, E., additional, Rodier, J.F., additional, Cutuli, B., additional, Lasry, S., additional, Mauriac, L., additional, Granon, C., additional, Kerr, C., additional, Giard, S., additional, Hill, C., additional, De Lafontan, B., additional, De Gislain, C., additional, D’Anjou, J., additional, Fondrinier, E., additional, Lefeuvre, C., additional, Lasset, C., additional, Bonadona, V., additional, and Chauvin, F., additional
Published: 1997
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87. Correlation between clinical response to interleukin 2 and HLA phenotypes in patients with metastatic renal cell carcinoma

Author: Bain, C, primary, Merrouche, Y, additional, Puisieux, I, additional, Blay, J-Y, additional, Negrier, S, additional, Bonadona, V, additional, Lasset, C, additional, Lanier, F, additional, Duc, A, additional, Gebuhrer, L, additional, Philip, T, additional, and Favrot, MC, additional
Published: 1997
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88. Patients' characteristics and rate of Internet use to obtain cancer information.

Author: Mancini J, Noguès C, Adenis C, Berthet P, Bonadona V, Chompret A, Coupier I, Eisinger F, Fricker JP, Gauthier-Villars M, Lasset C, Lortholary A, N'Guyen TD, Vennin P, Sobol H, Stoppa-Lyonnet D, and Julian-Reynier C
Abstract: The aim of this study was to present baseline data on the access to Internet by French breast cancer patients attending genetic clinics and to examine factors affecting Internet health-related use. Twenty-four percent of participants used Internet to obtain information about the disease. This rate was higher among patients with health occupations [adjusted odds ratio (adjOR) 2.6; 95% confidence interval (CI) 1.3-5.1], the most highly educated (adjOR 2.1; 95% CI 1.1-4.0) and those under 41 years of age (adjOR 7.3; 95% CI 2.1-26.2). Almost one of every three women was dissatisfied of this source of information. [ABSTRACT FROM AUTHOR]
Published: 2006
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89. BRAF as a melanoma susceptibility candidate gene?

Author: Laud, K., Kannengiesser, C., Avril, M. -F, Chompret, A., Stoppa-Lyonnet, D., Desjardins, L., Alain EYCHENE, Demenais, F., Andry-Benzaquen, P., Baccard, M., Bachollet, B., Basset-Seguin, N., Baspeyras, M., Berthet, P., Bonnetblanc, J. -M, Blanchet, P., Boitier, F., Bonadona, V., Caux, F., Cesarini, J. -P, Chevrant-Breton, J., Couillet, D., Courouge-Dorcier, A. -M, Demange, L., Levy, C., Dereure, O., D Incan, M., Dore, M., Esteve, E., Frenay, M., Gaillard, V., Gorin, I., Grange, F., Guillot, B., Joly, P., Laroche, L., Lasset, C., Leroux, D., Limacher, J. -M, Longy, M., Lumbroso, L., Michel, J. -L, Negrier, S., Ollivaud, L., Ortoli, J. -C, Robin, P., Sassolas, B., Triller, R., Truchetet, F., Vabres, P., Verne, L., Lenoir, G. M., and Bressac-De Paillerets, B.

90. Cancer patients who experienced diagnostic genetic testing for cancer susceptibility: reactions and behavior after the disclosure of a positive test result

Author: Bonadona V, Saltel P, Desseigne F, Mignotte H, Jc, Saurin, Wang Q, Sinilnikova O, Giraud S, Freyer G, Plauchu H, Alain PUISIEUX, Lasset C, 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), and 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)
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT]

91. Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression

Author: Schoof, N, Iles, Mm, Bishop, Dt, Newton Bishop JA, Barrett, Jh, Mann, Gj, Hopper, Jl, Aitken, Jf, Armstrong, Bk, Giles, Gg, Kefford, Rf, Cust, A, Jenkins, M, Aguilera, P, Badenas, C, Carrera, C, Cuellar, F, Gabriel, D, Martinez, E, Gonzalez, M, Iglesias, P, Malvehy, J, Marti Laborda, R, Mila, M, Ogbah, Z, Butille, Ja, Puig, S, Alós, L, Arance, A, Arguís, P, Campo, A, Castel, T, Conill, C, Palou, J, Rull, R, Sánchez, M, Vidal Sicart, S, Vilalta, A, Vilella, R, Martin, Ng, Montgomery, Gw, Duffy, D, Whiteman, D, Macgregor, S, Hayward, Nk, Webb, P, Parsons, P, Purdie, D, Hayward, N, Landi, Mt, Calista, D, Landi, G, Minghetti, P, Arcangeli, F, Bertazzi, Pa, Bianchi, Giovanna, Ghiorzo, Paola, Pastorino, Lorenza, Bruno, William, Battistuzzi, Linda, Gargiulo, Sara, Nasti, Sabina, Gliori, S, Origone, Paola, Queirolo, P, Mackie, R, Lang, J, Bishop, Ja, Affleck, P, Harrison, J, Randerson Moor, J, Harland, M, Taylor, Jc, Whittaker, L, Kukalizch, K, Leake, S, Karpavicius, B, Haynes, S, Mack, T, Chan, M, Taylor, Y, Davies, J, King, P, Gruis, Na, van Nieuwpoort FA, Out, C, van der Drift, C, Bergman, W, Kukutsch, N, Bavinck, Jn, Bakker, B, van der Stoep, N, ter Huurne, J, van der Rhee, H, Bekkenk, M, Snels, D, van Praag, M, Brochez, L, Gerritsen, R, Crijns, M, Vasen, H, Olsson, H, Ingvar, C, Jönsson, G, Borg, Å, Måsbäck, A, Lundgren, L, Baeckenhorn, K, Nielsen, K, Casslén, As, Helsing, P, Andresen, Pa, Rootwelt, H, Akslen, La, Molven, A, Avril, Mf, Bressac de Paillerets, B, Chaudru, V, Chateigner, N, Corda, E, Jeannin, P, Lesueur, F, de Lichy, M, Maubec, E, Mohamdi, H, Demenais, F, Andry Benzaquen, P, Bachollet, B, Bérard, F, Berthet, P, Boitier, F, Bonadona, V, Bonafé, Jl, Bonnetblanc, Jm, Cambazard, F, Caron, O, Caux, F, Chevrant Breton, J, Chompret, A, Dalle, S, Demange, L, Dereure, O, Doré, Mx, Doutre, Ms, Dugast, C, Faivre, L, Grange, F, Humbert, P, Joly, P, Kerob, D, Lasset, C, Leccia, Mt, Lenoir, G, Leroux, D, Levang, J, Lipsker, D, Mansard, S, Martin, L, Martin Denavit, T, Mateus, C, Michel, Jl, Morel, P, Olivier Faivre, L, Perrot, Jl, Robert, C, Ronger Savle, S, Sassolas, B, Souteyrand, P, Stoppa Lyonnet, D, Thomas, L, Vabres, P, Wierzbicka, E, Elder, D, Kanetsky, P, Knorr, J, Ming, M, Mitra, N, Ruffin, A, Van Belle, P, Dębniak, T, Lubiński, J, Mirecka, A, Ertmański, S, Novakovic, S, Hocevar, M, Peric, B, Cerkovnik, P, Höiom, V, Hansson, J, Schmid, H, Holland, Ea, Azizi, E, Galore Haskel, G, Friedman, E, Baron Epel, O, Scope, A, Pavlotsky, F, Yakobson, E, Cohen Manheim, I, Laitman, Y, Milgrom, R, Shimoni, I, Kozlovaa, E., 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 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), Martí Laborda, Rosa Ma., and Universitat de Barcelona
Subjects: Melanomas, Skin Neoplasms, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, Genome-wide association study, 0302 clinical medicine, Polymorphism (computer science), Genetics of the Immune System, lcsh:Science, Melanoma, Genetics, 0303 health sciences, Multidisciplinary, Cancer Risk Factors, Statistics, Immunosuppression, Genomics, Oncology, Genetic Epidemiology, 030220 oncology & carcinogenesis, Medicine, Research Article, medicine.medical_specialty, Immunology, Genetic Causes of Cancer, Malignant Skin Neoplasms, Single-nucleotide polymorphism, Dermatology, Biostatistics, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Genome Analysis Tools, Molecular genetics, Genome-Wide Association Studies, medicine, Humans, SNP, Genetic Predisposition to Disease, Statistical Methods, Gene, 030304 developmental biology, Immunosuppression Therapy, Evolutionary Biology, Population Biology, Immunosupressió, lcsh:R, Computational Biology, Human Genetics, medicine.disease, Genetic Polymorphism, Clinical Immunology, lcsh:Q, Population Genetics, Mathematics, Genome-Wide Association Study
Abstract: Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (pemp = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (pemp = 0.006) and secretion of suppressive factors (pemp = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.
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92. Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study

Author: Seçil Aksoy, Michael O. Woods, Heinric Williams, Bruno Buecher, Finlay A. Macrae, Lotte N. Krogh, Jay Qiu, Wan K.W. Juhari, Jan T. Lowery, Anne-Marie Gerdes, Magnus von Knebel Doeberitz, Luigi Ricciardiello, Karsten Schulmann, Jose Luis Soto, Kristina Lagerstedt-Robinson, Kiwamu Akagi, Raj Ramesar, Uffe Birk Jensen, Angel Alonso, Robert Hüneburg, Olivier Caron, Michel Longy, Jan Lubinski, Kate Green, Annabel Goodwin, D. Gareth Evans, Julie Wods, Leigha Senter, Matthew F. Kalady, Mark Clendenning, Barbara A. Leggett, Ravindran Ankathil, Swati G. Patel, Julian Barwell, Katherine M. Tucker, Grant Lee, Pascaline Berthet, Dawn M. Nixon, Sonia S. Kupfer, Naohiro Tomita, Susan Parry, Trinidad Caldés, Robert W. Haile, Edenir Inêz Palmero, Karin Alvarez, Cassandra B. Nichols, Mark A. Jenkins, N. Jewel Samadder, Loic LeMarchand, John Burn, Francisco Lopez, Rodney J. Scott, Pierre Laurent-Puig, Julie Arnold, Christina Therkildsen, Hans K. Schackert, Pilar Garre, Reinhard Buettner, Adriana Della Valle, Patricia Esperon, Wolff Schmiegel, Karl Heinimann, Inge Bernstein, Matthias Kloor, Nicoline Hoogerbrugge, Rui Manuel Reis, Fränzel J.B. Van Duijnhoven, Christoph Engel, Mohd Nizam Zahary, Sylviane Olschwang, Sapna Syngal, Valérie Bonadona, Nicholas Pachter, Matilde Navarro, Albert de la Chapelle, Beate Betz, Jukka-Pekka Mecklin, Catherine Noguès, Elena M. Stoffel, Toni T. Seppälä, Chrystelle Colas, Anneke Lucassen, Allan D. Spigelman, Youenn Drouet, Elisa J. Cops, Uri Ladabaum, Steve Thibodeau, Jeffrey N. Weitzel, Fiona Lalloo, Patrick J. Morrison, Maurizio Genuardi, Kohji Tanakaya, Patrick M. Lynch, Frederik J. Hes, William D. Foulkes, Carmen Guillén-Ponce, Jenny von Salomé, Emilia Rogoża-Janiszewska, Andrew Latchford, John L. Hopper, Carrie Snyder, Verónica Barca-Tierno, Gabriela Möslein, Lauren M. Gima, Melissa C. Southey, Paul A. James, Marion Dhooge, Claudia Perne, Steven Gallinger, Heather Hampel, Amanda B. Spurdle, Ingrid Winship, Emmanuelle Fourme, Rish K. Pai, Daniela Turchetti, Marta Pineda, Jürgen Weitz, James Hill, Daniel D. Buchanan, Carlos A. Vaccaro, Noralane M. Lindor, Rachel Pearlman, Pål Møller, Christian P. Strassburg, Jane C. Figueiredo, Aída Falcón de Vargas, Silke Zachariae, Karolin Bucksch, Joanne Ngeow, Silke Redler, Henrik Okkels, Maija R.J. Kohonen-Corish, Hans F. A. Vasen, Verena Steinke-Lange, Roselyne Guimbaud, Deepak Vangala, Isabelle Coupier, Nils Rahner, Berrin Tunca, Sanne W. Bajwa-ten Broeke, Niels de Wind, Sophie Lejeune, José Gaston Guillem, Karin Wadt, Polly A. Newcomb, Elke Holinski-Feder, Florencia Neffa, Rodrigo Santa Cruz Guindalini, Paul E. Wise, Julian R. Sampson, Graham Casey, Lene Juel Rasmussen, Rolf H. Sijmons, Tadeusz Dębniak, Ann-Sofie Backman, Joji Utsunomiya, Melyssa Aronson, Aung Ko Win, Yves-Jean Bignon, Judy W. C. Ho, Robyn L. Ward, Mev Dominguez-Valentin, Karolina Malińska, Elizabeth E. Half, John-Paul Plazzer, Marjolijn J. L. Ligtenberg, Rachel Austin, Nicola K. Poplawski, Marcia Cruz-Correa, Nagahide Matsubara, Charlotte Kvist Lautrup, Thomas Hansen, Tatsuro Yamaguchi, Thomas John, David J. Amor, Ilana Solomon, Yun-Hee Choi, Meghan J. van Wanzeele, Rakefet Shtoyerman, Vanessa Huntley, Maartje Nielsen, Deborah Neklason, Kevin J. Monahan, Gülçin Tezcan, Stefan Aretz, Talya Boisjoli, Sophie Giraud, Thierry Frebourg, Christophe Rosty, Heike Görgens, Lone Sunde, Allyson Templeton, Jacob Nattermann, Mala Pande, Joan Brunet, Nancy Uhrhammer, James M. Church, Florencia Spirandelli, Laurent Briollais, James G. Dowty, Jeanette C. Reece, Rachel Susman, Fay Kastrinos, Kirsi Pylvänäinen, Gabriel Capellá, Helène Schuster, Min H. Chew, Markus Loeffler, Christine Lasset, Michael J. Hall, Capuccine Delnatte, Floor A. Duijkers, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Digital Precision Cancer Medicine (iCAN), ATG - Applied Tumor Genomics, HUS Abdominal Center, Clinical sciences, Medical Genetics, Win A.K., Dowty J.G., Reece J.C., Lee G., Templeton A.S., Plazzer J.-P., Buchanan D.D., Akagi K., Aksoy S., Alonso A., Alvarez K., Amor D.J., Ankathil R., Aretz S., Arnold J.L., Aronson M., Austin R., Backman A.-S., Bajwa-ten Broeke S.W., Barca-Tierno V., Barwell J., Bernstein I., Berthet P., Betz B., Bignon Y.-J., Boisjoli T., Bonadona V., Briollais L., Brunet J., Bucksch K., Buecher B., Buettner R., Burn J., Caldes T., Capella G., Caron O., Casey G., Chew M.H., Choi Y.-H., Church J., Clendenning M., Colas C., Cops E.J., Coupier I., Cruz-Correa M., de la Chapelle A., de Wind N., Debniak T., Della Valle A., Delnatte C., Dhooge M., Dominguez-Valentin M., Drouet Y., Duijkers F.A., Engel C., Esperon P., Evans D.G., Falcon de Vargas A., Figueiredo J.C., Foulkes W., Fourme E., Frebourg T., Gallinger S., Garre P., Genuardi M., Gerdes A.-M., Gima L.M., Giraud S., Goodwin A., Gorgens H., Green K., Guillem J., Guillen-Ponce C., Guimbaud R., Guindalini R.S.C., Half E.E., Hall M.J., Hampel H., Hansen T.V.O., Heinimann K., Hes F.J., Hill J., Ho J.W.C., Holinski-Feder E., Hoogerbrugge N., Huneburg R., Huntley V., James P.A., Jensen U.B., John T., Juhari W.K.W., Kalady M., Kastrinos F., Kloor M., Kohonen-Corish M.R., Krogh L.N., Kupfer S.S., Ladabaum U., Lagerstedt-Robinson K., Lalloo F., Lasset C., Latchford A., Laurent-Puig P., Lautrup C.K., Leggett B.A., Lejeune S., LeMarchand L., Ligtenberg M., Lindor N., Loeffler M., Longy M., Lopez F., Lowery J., Lubinski J., Lucassen A.M., Lynch P.M., Malinska K., Matsubara N., Mecklin J.-P., Moller P., Monahan K., Morrison P.J., Nattermann J., Navarro M., Neffa F., Neklason D., Newcomb P.A., Ngeow J., Nichols C., Nielsen M., Nixon D.M., Nogues C., Okkels H., Olschwang S., Pachter N., Pai R.K., Palmero E.I., Pande M., Parry S., Patel S.G., Pearlman R., Perne C., Pineda M., Poplawski N.K., Pylvanainen K., Qiu J., Rahner N., Ramesar R., Rasmussen L.J., Redler S., Reis R.M., Ricciardiello L., Rogoza-Janiszewska E., Rosty C., Samadder N.J., Sampson J.R., Schackert H.K., Schmiegel W., Schulmann K., Schuster H., Scott R., Senter L., Seppala T.T., Shtoyerman R., Sijmons R.H., Snyder C., Solomon I.B., Soto J.L., Southey M.C., Spigelman A., Spirandelli F., Spurdle A.B., Steinke-Lange V., Stoffel E.M., Strassburg C.P., Sunde L., Susman R., Syngal S., Tanakaya K., Tezcan G., Therkildsen C., Thibodeau S., Tomita N., Tucker K.M., Tunca B., Turchetti D., Uhrhammer N., Utsunomiya J., Vaccaro C., van Duijnhoven F.J.B., van Wanzeele M.J., Vangala D.B., Vasen H.F.A., von Knebel Doeberitz M., von Salome J., Wadt K.A.W., Ward R.L., Weitz J., Weitzel J.N., Williams H., Winship I., Wise P.E., Wods J., Woods M.O., Yamaguchi T., Zachariae S., Zahary M.N., Hopper J.L., Haile R.W., Macrae F.A., Moslein G., and Jenkins M.A.
Subjects: 0301 basic medicine, Proband, Oncology, Male, Heredity, DNA mismatch repair, [SDV]Life Sciences [q-bio], SUSCEPTIBILITY, Settore MED/03 - GENETICA MEDICA, 0302 clinical medicine, Residence Characteristics, Risk Factors, Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14], PMS2, ComputingMilieux_MISCELLANEOUS, MLH1, Age Factors, Middle Aged, Penetrance, Lynch syndrome, 3. Good health, Pedigree, Phenotype, 030220 oncology & carcinogenesis, Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis, Female, Adult, medicine.medical_specialty, PENETRANCE, congenital, hereditary, and neonatal diseases and abnormalities, GENES, 3122 Cancers, colorectal cancer, BREAST, Risk Assessment, 03 medical and health sciences, Sex Factors, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Retrospective Studies, business.industry, MUTATIONS, Cancer, medicine.disease, digestive system diseases, MSH2, MSH6, MODEL, INDIVIDUALS, 030104 developmental biology, Lynch Syndrome, Gene-Environment Interaction, business
Abstract: Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (p 0 center dot 0001 for each of the three three continents). These familial risk factors resulted in a wide within-gene variation in the risk of colorectal cancer for men and women from each continent who all carried pathogenic variants in the same gene or the MSH2 c.942+3A T variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and onlyBackground Existing clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence. Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero. Findings 5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australasia. There was strong evidence of the existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers (pT variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7-56% of carriers having a colorectal cancer penetrance of less than 20%, 9-44% having a penetrance of more than 80%, and only 10-19% having a penetrance of 40-60%. Interpretation Our study findings highlight the important role of risk modifiers, which could lead to personalised risk assessments for precision prevention and early detection of colorectal cancer for people with Lynch syndrome. Funding National Health and Medical Research Council, Australia. Copyright (c) 2021 Elsevier Ltd. All rights reserved.Methods In this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero.
Published: 2021
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93. Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

Author: Thomas v O Hansen, Amanda B. Spurdle, Anne-Marie Gerdes, Sue Healey, Per Karlsson, Tomasz Huzarski, Mary B. Daly, Mary Porteous, T. Caldes, Ulf Kristoffersson, Ignacio Blanco, A. Miron, Laurence Faivre, Barbara Wappenschmidt, Laurence Venat-Bouvet, Marie Stenmark Askmalm, Olga M. Sinilnikova, Susan Peock, Alessandra Viel, Conxi Lázaro, Katherine L. Nathanson, Laurent Castera, Douglas F. Easton, Susan L. Neuhausen, Jan Lubinski, Phuong L. Mai, Virginie Moncoutier, Paolo Radice, Heli Nevanlinna, Christi J Asperen, Xianshu Wang, Brita Arver, Christian Sutter, Senno Verhoef, Rosette Lidereau, Mary S Beattie, Bjarni A Agnarsson, Ina Ruehl, Monica Barile, Bent Ejlertsen, Laura Ottini, Catherine Noguès, Jennifer A. Przybylo, Cinzia Casella, Trevor Cole, Norbert Arnold, Sandra Fert-Ferrer, Hilmi Ozcelik, Irene L. Andrulis, Susan M. Domchek, Valérie Bonadona, Kirsten B. Moysich, David E. Goldgar, Anna Jakubowska, Paul D.P. Pharoah, Beth Y. Karlan, Jenny Gross, Gaia Roversi, Tadeusz Dębniak, Hanne Meijers-Heijboer, Susan J. Ramus, Dorthe G. Crüger, Zachary S. Fredericksen, Siranoush Manoukian, Viviana Gismondi, Maria A. Caligo, Helene Holland, Laure Barjhoux, Gord Glendon, Ana Osorio, Jacques Simard, John L. Hopper, Mercedes Durán, Kristiina Aittomäki, Håkan Olsson, Mads Thomassen, Fabio Capra, Patrick J. Morrison, Britta Fiebig, Mary Beth Terry, Marinus J. Blok, Evgeny N. Imyanitov, Joseph Vijai, Javier Benitez, Mark T. Rogers, D. Gareth Evans, Helmut Deissler, Tomasz Byrski, Sylvie Mazoyer, Laura Papi, Dominique Stoppa-Lyonnet, Marco Montagna, Kenneth Offit, Cezary Cybulski, Dominique Leroux, Georgia Chenevix-Trench, Danielle Bodmer, Lucy Side, Margaret Cook, Ros Eeles, Alan Donaldson, Christiana Kartsonaki, Carole Brewer, Matti A. Rookus, Jacek Gronwald, Dorothea Gadzicki, Shirley Hodgson, Jonathan Beesley, Gabriella Pichert, Andrew K. Godwin, Dieter Niederacher, Yuan Chun Ding, Torben A Kruse, Paolo Peterlongo, Rita K. Schmutzler, Xiaoqing Chen, Annika Lindblom, Fergus J. Couch, Maaike P.G. Vreeswijk, Mark H. Greene, Esther M. John, Raymonda Varon-Mateeva, Simon A. Gayther, Margreet G. E. M. Ausems, Tomas Kirchhoff, Lars Jønson, Madeleine M. A. Tilanus-Linthorst, Ute Hamann, Marie-Agnès Collonge-Rame, Antonis C. Antoniou, M John Kennedy, Karin Kast, Theo A. M. van Os, Penny Soucy, Debra Frost, Alison M. Dunning, Daniela Zaffaroni, Anna Allavena, Maria-Isabel Tejada, Yves-Jean Bignon, Lesley McGuffog, Bohdan Górski, Åke Borg, Fabienne Prieur, Bernard Peissel, Helen Gregory, Clare Oliver, Saundra S. Buys, Ana Dutra-Clarke, Alfons Meindl, Ramunas Janavicius, Uffe Birk Jensen, Miguel de la Hoya, Ramus, S, Kartsonaki, C, Gayther, S, Pharoah, P, Sinilnikova, O, Beesley, J, Chen, X, Mcguffog, L, Healey, S, Couch, F, Wang, X, Fredericksen, Z, Peterlongo, P, Manoukian, S, Peissel, B, Zaffaroni, D, Roversi, G, Barile, M, Viel, A, Allavena, A, Ottini, L, Papi, L, Gismondi, V, Capra, F, Radice, P, Greene, M, Mai, P, Andrulis, I, Glendon, G, Ozcelik, H, Thomassen, M, Gerdes, A, Kruse, T, Cruger, D, Jensen, U, Caligo, M, Olsson, H, Kristoffersson, U, Lindblom, A, Arver, B, Karlsson, P, Stenmark Askmalm, M, Borg, A, Neuhausen, S, Ding, Y, Nathanson, K, Domchek, S, Jakubowska, A, Lubiński, J, Huzarski, T, Byrski, T, Gronwald, J, Górski, B, Cybulski, C, Dębniak, T, Osorio, A, Durán, M, Tejada, M, Benítez, J, Hamann, U, Rookus, M, Verhoef, S, Tilanus Linthorst, M, Vreeswijk, M, Bodmer, D, Ausems, M, van Os, T, Asperen, C, Blok, M, Meijers Heijboer, H, Peock, S, Cook, M, Oliver, C, Frost, D, Dunning, A, Evans, D, Eeles, R, Pichert, G, Cole, T, Hodgson, S, Brewer, C, Morrison, P, Porteous, M, Kennedy, M, Rogers, M, Side, L, Donaldson, A, Gregory, H, Godwin, A, Stoppa Lyonnet, D, Moncoutier, V, Castera, L, Mazoyer, S, Barjhoux, L, Bonadona, V, Leroux, D, Faivre, L, Lidereau, R, Nogues, C, Bignon, Y, Prieur, F, Collonge Rame, M, Venat Bouvet, L, Fert Ferrer, S, Miron, A, Buys, S, Hopper, J, Daly, M, John, E, Terry, M, Goldgar, D, Hansen, T, Jønson, L, Ejlertsen, B, Agnarsson, B, Offit, K, Kirchhoff, T, Vijai, J, Dutra Clarke, A, Przybylo, J, Montagna, M, Casella, C, Imyanitov, E, Janavicius, R, Blanco, I, Lázaro, C, Moysich, K, Karlan, B, Gross, J, Beattie, M, Schmutzler, R, Wappenschmidt, B, Meindl, A, Ruehl, I, Fiebig, B, Sutter, C, Arnold, N, Deissler, H, Varon Mateeva, R, Kast, K, Niederacher, D, Gadzicki, D, Caldes, T, de la Hoya, M, Nevanlinna, H, Aittomäki, K, Simard, J, Soucy, P, Spurdle, A, Holland, H, Chenevix Trench, G, Easton, D, Antoniou, A, Faculteit Medische Wetenschappen/UMCG, 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 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), Klinische Genetica, Genetica & Celbiologie, RS: GROW - School for Oncology and Reproduction, Clinical Genetics, Pediatric Surgery, Human genetics, CCA - Oncogenesis, and Human Genetics
Subjects: Oncology, Cancer Research, endocrine system diseases, Genes, BRCA2, Genes, BRCA1, Genome-wide association study, FAMILIES, 0302 clinical medicine, Risk Factors, Retrospective Studie, Genotype, Odds Ratio, skin and connective tissue diseases, POPULATION, Genetics, Ovarian Neoplasms, Aged, 80 and over, Allele, 0303 health sciences, education.field_of_study, Likelihood Functions, Articles, GERMLINE MUTATIONS, Middle Aged, Likelihood Function, female genital diseases and pregnancy complications, 3. Good health, 030220 oncology & carcinogenesis, Female, Chromosomes, Human, Pair 9, Human, Adult, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], medicine.medical_specialty, Heterozygote, SUSCEPTIBILITY LOCI, PROTEINS, Population, Biology, Polymorphism, Single Nucleotide, BASONUCLIN-2, 03 medical and health sciences, Breast cancer, Germline mutation, SDG 3 - Good Health and Well-being, Internal medicine, medicine, BREAST-CANCER, Humans, GENOME-WIDE ASSOCIATION, education, Alleles, Germ-Line Mutation, 030304 developmental biology, Retrospective Studies, Aged, IDENTIFICATION, Risk Factor, Ovarian Neoplasm, Editorials, Cancer, medicine.disease, Minor allele frequency, Ovarian cancer
Abstract: [Background]: Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2. [Methods]: We genotyped rs3814113 in 10 029 BRCA1 mutation carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided. [Results]: The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 × 10-9) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 × 10-4). This SNP was not associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers. BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to have an ovarian cancer risk to age 80 years of 48%, and those with the CC genotype were predicted to have a risk of 33%. [Conclusion]: Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a BRCA1 or BRCA2 mutation., Spanish National Cancer Center (CNIO) and the Spanish Consortium: Partially supported by Fundación Mutua Madrileña, Asociación Española Contra el Cáncer, and the Spanish Ministry of Science and Innovation (FIS PI08 1120).
Published: 2011
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94. Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Author: Kuchenbaecker, Karoline B, Neuhausen, Susan L, Robson, Mark, Barrowdale, Daniel, McGuffog, Lesley, Mulligan, Anna Marie, Andrulis, Irene L, Spurdle, Amanda B, Schmidt, Marjanka K, Schmutzler, Rita K, Engel, Christoph, Wappenschmidt, Barbara, Nevanlinna, Heli, Thomassen, Mads, Southey, Melissa, Radice, Paolo, Ramus, Susan J, Domchek, Susan M, Nathanson, Katherine L, Lee, Andrew, Healey, Sue, Nussbaum, Robert L, Rebbeck, Timothy R, Arun, Banu K, James, Paul, Karlan, Beth Y, Lester, Jenny, Cass, Ilana, Breast Cancer Family Registry, the, Terry, Mary Beth, Daly, Mary B, Goldgar, David E, Buys, Saundra S, Janavicius, Ramunas, Tihomirova, Laima, Tung, Nadine, Dorfling, Cecilia M, van Rensburg, Elizabeth J, Steele, Linda, v O Hansen, Thomas, Ejlertsen, Bent, Gerdes, Anne-Marie, Nielsen, Finn C, Dennis, Joe, Cunningham, Julie, Hart, Steven, Slager, Susan, Osorio, Ana, Benitez, Javier, Duran, Mercedes, Weitzel, Jeffrey N, Tafur, Isaac, Hander, Mary, Peterlongo, Paolo, Manoukian, Siranoush, Peissel, Bernard, Roversi, Gaia, Scuvera, Giulietta, Bonanni, Bernardo, Mariani, Paolo, Volorio, Sara, Dolcetti, Riccardo, Varesco, Liliana, Papi, Laura, Tibiletti, Maria Grazia, Giannini, Giuseppe, Fostira, Florentia, Konstantopoulou, Irene, Garber, Judy, Hamann, Ute, Donaldson, Alan, Brewer, Carole, Foo, Claire, Evans, D Gareth, Frost, Debra, Eccles, Diana, EMBRACE Study, the, Douglas, Fiona, Brady, Angela, Cook, Jackie, Tischkowitz, Marc, Adlard, Julian, Barwell, Julian, Ong, Kai-ren, Walker, Lisa, Izatt, Louise, Side, Lucy E, Kennedy, M John, Rogers, Mark T, Porteous, Mary E, Morrison, Patrick J, Platte, Radka, Eeles, Ros, Davidson, Rosemarie, Hodgson, Shirley, Ellis, Steve, Godwin, Andrew K, Rhiem, Kerstin, Meindl, Alfons, Ditsch, Nina, Arnold, Norbert, Plendl, Hansjoerg, Niederacher, Dieter, Sutter, Christian, Steinemann, Doris, Bogdanova-Markov, Nadja, Kast, Karin, Varon-Mateeva, Raymonda, Wang-Gohrke, Shan, Gehrig, Andrea, Markiefka, Birgid, Buecher, Bruno, Lefol, Cédrick, Stoppa-Lyonnet, Dominique, Rouleau, Etienne, Prieur, Fabienne, Damiola, Francesca, GEMO Study Collaborators, the, Barjhoux, Laure, Faivre, Laurence, Longy, Michel, Sevenet, Nicolas, Sinilnikova, Olga M, Mazoyer, Sylvie, Bonadona, Valérie, Caux-Moncoutier, Virginie, Isaacs, Claudine, Van Maerken, Tom, Claes, Kathleen, Piedmonte, Marion, Andrews, Lesley, Hays, John, Rodriguez, Gustavo C, Caldes, Trinidad, de la Hoya, Miguel, Khan, Sofia, Hogervorst, Frans BL, Aalfs, Cora M, de Lange, JL, Meijers-Heijboer, Hanne EJ, van der Hout, Annemarie H, Wijnen, Juul T, van Roozendaal, KEP, Mensenkamp, Arjen R, van den Ouweland, Ans MW, van Deurzen, Carolien HM, van der Luijt, Rob B, HEBON, ., Olah, Edith, Diez, Orland, Lazaro, Conxi, Blanco, Ignacio, Teulé, Alex, Menendez, Mireia, Jakubowska, Anna, Lubinski, Jan, Cybulski, Cezary, Gronwald, Jacek, Jaworska-Bieniek, Katarzyna, Durda, Katarzyna, Arason, Adalgeir, Maugard, Christine, Soucy, Penny, Montagna, Marco, Agata, Simona, Teixeira, Manuel R, KConFab Investigators, the, Olswold, Curtis, Lindor, Noralane, Pankratz, Vernon S, Hallberg, Emily, Wang, Xianshu, Szabo, Csilla I, Vijai, Joseph, Jacobs, Lauren, Corines, Marina, Lincoln, Anne, Berger, Andreas, Fink-Retter, Anneliese, Singer, Christian F, Rappaport, Christine, Gschwantler Kaulich, Daphne, Pfeiler, Georg, Tea, Muy-Kheng, Phelan, Catherine M, Mai, Phuong L, Greene, Mark H, Rennert, Gad, Imyanitov, Evgeny N, Glendon, Gord, Toland, Amanda Ewart, Bojesen, Anders, Pedersen, Inge Sokilde, Jensen, Uffe Birk, Caligo, Maria A, Friedman, Eitan, Berger, Raanan, Laitman, Yael, Rantala, Johanna, Arver, Brita, Loman, Niklas, Borg, Ake, Ehrencrona, Hans, Olopade, Olufunmilayo I, Simard, Jacques, Easton, Douglas F, Chenevix-Trench, Georgia, Offit, Kenneth, Couch, Fergus J, Antoniou, Antonis C, CIMBA, on behalf of, Kuchenbaecker, K, Neuhausen, S, Robson, M, Barrowdale, D, Mcguffog, L, Mulligan, A, Andrulis, I, Spurdle, A, Schmidt, M, Schmutzler, R, Engel, C, Wappenschmidt, B, Nevanlinna, H, Thomassen, M, Southey, M, Radice, P, Ramus, S, Domchek, S, Nathanson, K, Lee, A, Healey, S, Nussbaum, R, Rebbeck, T, Arun, B, James, P, Karlan, B, Lester, J, Cass, I, Breast Cancer Family, R, Terry, M, Daly, M, Goldgar, D, Buys, S, Janavicius, R, Tihomirova, L, Tung, N, Dorfling, C, van Rensburg, E, Steele, L, v. O. Hansen, T, Ejlertsen, B, Gerdes, A, Nielsen, F, Dennis, J, Cunningham, J, Hart, S, Slager, S, Osorio, A, Benitez, J, Duran, M, Weitzel, J, Tafur, I, Hander, M, Peterlongo, P, Manoukian, S, Peissel, B, Roversi, G, Scuvera, G, Bonanni, B, Mariani, P, Volorio, S, Dolcetti, R, Varesco, L, Papi, L, Tibiletti, M, Giannini, G, Fostira, F, Konstantopoulou, I, Garber, J, Hamann, U, Donaldson, A, Brewer, C, Foo, C, Evans, D, Frost, D, Eccles, D, Embrace, S, Douglas, F, Brady, A, Cook, J, Tischkowitz, M, Adlard, J, Barwell, J, Ong, K, Walker, L, Izatt, L, Side, L, Kennedy, M, Rogers, M, Porteous, M, Morrison, P, Platte, R, Eeles, R, Davidson, R, Hodgson, S, Ellis, S, Godwin, A, Rhiem, K, Meindl, A, Ditsch, N, Arnold, N, Plendl, H, Niederacher, D, Sutter, C, Steinemann, D, Bogdanova Markov, N, Kast, K, Varon Mateeva, R, Wang Gohrke, S, Gehrig, A, Markiefka, B, Buecher, B, Lefol, C, Stoppa Lyonnet, D, Rouleau, E, Prieur, F, Damiola, F, GEMO Study, C, Barjhoux, L, Faivre, L, Longy, M, Sevenet, N, Sinilnikova, O, Mazoyer, S, Bonadona, V, Caux Moncoutier, V, Isaacs, C, Van Maerken, T, Claes, K, Piedmonte, M, Andrews, L, Hays, J, Rodriguez, G, Caldes, T, de la Hoya, M, Khan, S, Hogervorst, F, Aalfs, C, de Lange, J, Meijers Heijboer, H, van der Hout, A, Wijnen, J, van Roozendaal, K, Mensenkamp, A, van den Ouweland, A, van Deurzen, C, van der Luijt, R, Hebon, Olah, E, Diez, O, Lazaro, C, Blanco, I, Teulé, A, Menendez, M, Jakubowska, A, Lubinski, J, Cybulski, C, Gronwald, J, Jaworska Bieniek, K, Durda, K, Arason, A, Maugard, C, Soucy, P, Montagna, M, Agata, S, Teixeira, M, Kconfab, I, Olswold, C, Lindor, N, Pankratz, V, Hallberg, E, Wang, X, Szabo, C, Vijai, J, Jacobs, L, Corines, M, Lincoln, A, Berger, A, Fink Retter, A, Singer, C, Rappaport, C, Kaulich, D, Pfeiler, G, Tea, M, Phelan, C, Mai, P, Greene, M, Rennert, G, Imyanitov, E, Glendon, G, Toland, A, Bojesen, A, Pedersen, I, Jensen, U, Caligo, M, Friedman, E, Berger, R, Laitman, Y, Rantala, J, Arver, B, Loman, N, Borg, A, Ehrencrona, H, Olopade, O, Simard, J, Easton, D, Chenevix Trench, G, Offit, K, Couch, F, Antoniou, A, Cimba, Lee, Andrew [0000-0003-0677-0252], Dennis, Joe [0000-0003-4591-1214], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Antoniou, Antonis [0000-0001-9223-3116], and Apollo - University of Cambridge Repository
Subjects: Cancer Research, Receptor, ErbB-2, Genes, BRCA2, BRCA, LOCI, Genes, BRCA1, MODIFIERS, VARIANTS, ErbB-2, 610 Medical sciences Medicine, Ductal, Receptors, Medicine and Health Sciences, INVESTIGATORS, Breast, skin and connective tissue diseases, Progesterone, Medicine(all), Carcinoma, Ductal, Breast, Middle Aged, Adult, Aged, Alleles, Breast Neoplasms, Carcinoma, Carcinoma, Lobular, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Neoplasm Grading, Neoplasm Staging, Receptors, Estrogen, Receptors, Progesterone, Oncology, TUMOR SUBTYPES, Receptor, Research Article, MEDULLARY CARCINOMA, OVARIAN-CANCER, Lobular, GENOME-WIDE ASSOCIATION, CONSORTIUM, BRCA1, Estrogen, BRCA2, ESTROGEN-RECEPTOR, Genes
Abstract: Introduction More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P
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95. Postzygotic mosaicism of SMARCB1 variants in patients with rhabdoid tumors: A not-so-rare condition exposing to successive tumors.

Author: Thomson G, Filser M, Guerrini-Rousseau L, Tauziede-Espariat A, Bourneix C, Gauthier-Villars M, Simaga F, Beccaria K, Faure-Conter C, Maureille A, Zattara-Cannoni H, Andre N, Entz-Werle N, Brugieres L, Mansuy L, Denizeau P, Julia S, Ingster O, Lejeune S, Brahimi A, Coupier I, Bonadona V, Delattre O, Masliah-Planchon J, and Bourdeaut F
Subjects: Humans, Male, Female, Child, Preschool, Infant, Child, High-Throughput Nucleotide Sequencing, Follow-Up Studies, Genetic Predisposition to Disease, Prognosis, Adolescent, Adult, Biomarkers, Tumor genetics, Infant, Newborn, SMARCB1 Protein genetics, Rhabdoid Tumor genetics, Mosaicism, Germ-Line Mutation
Abstract: Background: Rhabdoid tumors (RT) are aggressive, rare tumors predominantly affecting young children, characterized by biallelic SMARCB1 gene inactivation. While most SMARCB1 alterations are acquired de novo, a third of cases exhibit germline alterations, defining Rhabdoid Tumors Predisposition Syndrome. With the increased sensitivity of next-generation sequencing (NGS), mosaicisms in genes linked to genetic diseases are more detectable. This study focuses on exploring SMARCB1 germline alterations, notably mosaicism in blood samples of children with RT and in parents, using a custom NGS panel., Methods: A cohort of 280 children and 140 parents with germline analysis was studied. Germline DNA from 111 children with RT and 32 parents were reanalyzed with a custom NGS panel with 1500X average depth targeting the SMARCB1 gene to identify intragenic variants not detected with conventional low-sensitivity methods. Follow-up data was obtained for 77 patients., Results: Nine previously undetected mosaicism cases were identified, totaling 17/280 patients with a mosaic variant (6.1%) in the cohort, with variant allele frequencies between 0.9% and 33%, thus highlighting the prior underestimation of its prevalence. Follow-up data showed that 4 out of 7 survivors with mosaic variants developed distinct novel tumors, 2 sharing SMARCB1 alterations with the initial tumor, emphasizing the potential clinical impact of SMARCB1 mosaicism., Conclusions: The hitherto underestimated rate of SMARCB1 mosaicism in RT underscores the need for optimized genetic counseling and oncological monitoring. The findings have significant medical implications, considering the dire prognosis of RT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Published: 2024
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96. Medulloblastomas with ELP1 pathogenic variants: A weakly penetrant syndrome with a restricted spectrum in a limited age window.

Author: Guerrini-Rousseau L, Masliah-Planchon J, Filser M, Tauziède-Espariat A, Entz-Werle N, Maugard CM, Hopman SMJ, Torrejon J, Gauthier-Villars M, Simaga F, Blauwblomme T, Beccaria K, Rouleau E, Dimaria M, Grill J, Abbou S, Claret B, Brugières L, Doz F, Bouchoucha Y, Faure-Conter C, Bonadona V, Mansuy L, de Carli E, Ingster O, Legrand C, Pagnier A, Berthet P, Bodet D, Julia S, Bertozzi AI, Wilems M, Maurage CA, Delattre O, Ayrault O, Dufour C, and Bourdeaut F
Abstract: Background: ELP1 pathogenic variants (PV) have been recently identified as the most frequent variants predisposing to Sonic Hedgehog (SHH) medulloblastomas (MB); however, guidelines are still lacking for genetic counseling in this new syndrome., Methods: We retrospectively reviewed clinical and genetic data of a French series of 29 ELP1 -mutated MB., Results: All patients developed SHH-MB, with a biallelic inactivation of PTCH1 found in 24 tumors. Other recurrent alterations encompassed the TP53 pathway and activation of MYCN/MYCL signaling. The median age at diagnosis was 7.3 years (range: 3-14). ELP1 -mutated MB behave as sporadic cases, with similar distribution within clinical and molecular risk groups and similar outcomes (5 y - OS = 86%); no unusual side effect of treatments was noticed. Remarkably, a germline ELP1 PV was identified in all patients with available constitutional DNA ( n = 26); moreover, all tested familial trio ( n = 11) revealed that the PVs were inherited. Two of the 26 index cases from the French series had a family history of MB; pedigrees from these patients and from 1 additional Dutch family suggested a weak penetrance. Apart from MB, no cancer was associated with ELP1 PVs; second tumors reported in 4 patients occurred within the irradiation fields, in the usual time-lapse for expected radiotherapy-induced neoplasms., Conclusions: The low penetrance, the "at risk' age window limited to childhood and the narrow tumor spectrum, question the actual benefit of genetic screening in these patients and their family. Our results suggest restricting ELP1 germline sequencing to patients with SHH-MB, depending on the parents" request., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
Published: 2024
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97. An Integrated Cancer Prevention Strategy: the Viewpoint of the Leon Berard Comprehensive Cancer Center Lyon, France.

Author: Fervers B, Pérol O, Lasset C, Moumjid N, Vidican P, Saintigny P, Tardy J, Biaudet J, Bonadona V, Triviaux D, Marijnen P, Mongondry R, Cattey-Javouhey A, Buono R, Bertrand A, Marec-Bérard P, Rousset-Jablonski C, Pilleul F, Christophe V, Girodet M, Praud D, Solodky ML, Crochet H, Achache A, Michallet M, Galvez C, Miermont A, Sebileau D, Zrounba P, Beaupère S, Philip T, and Blay JY
Subjects: Humans, France epidemiology, Cancer Care Facilities, Delivery of Health Care, Neoplasms prevention & control
Abstract: This article describes some of the key prevention services in the Leon Berard Comprehensive Cancer Center (CLB) Lyon, France, which are based on clinical prevention services, outreach activities, and collaboration with professional and territorial health communities. In addition, research is embedded at all stages of the prevention continuum, from understanding cancer causes through to the implementation of prevention interventions during and after cancer. Health promotion activities in the community and dedicated outpatient primary cancer prevention services for individuals at increased risk have been implemented. The CLB's experience illustrates how prevention can be integrated into the comprehensive mission of cancer centers, and how in turn, the cancer centers may contribute to bridging the current fragmentation between cancer care and the different components of primary, secondary, and tertiary prevention. With increasing cancer incidence, the shift toward integrated prevention-centered cancer care is not only key for improving population health, but this may also provide a response to the shortage of hospital staff and overcrowding in cancer services, as well as offer opportunities to reduce carbon emissions from cancer care., (©2024 The Authors; Published by the American Association for Cancer Research.)
Published: 2024
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98. Overview of the Genetic Causes of Hereditary Breast and Ovarian Cancer Syndrome in a Large French Patient Cohort.

Author: Bouras A, Guidara S, Leone M, Buisson A, Martin-Denavit T, Dussart S, Lasset C, Giraud S, Bonnet-Dupeyron MN, Kherraf ZE, Sanlaville D, Fert-Ferrer S, Lebrun M, Bonadona V, Calender A, and Boutry-Kryza N
Abstract: The use of multigene panel testing for patients with a predisposition to Hereditary Breast and Ovarian Cancer syndrome (HBOC) is increasing as the identification of mutations is useful for diagnosis and disease management. Here, we conducted a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in 4630 French HBOC suspected patients. Patients were investigated using a germline cancer panel including the 13 genes defined by The French Genetic and Cancer Group (GGC)-Unicancer. In the patients analyzed, 528 pathogenic and likely pathogenic variants (P/LP) were identified, including BRCA1 (n = 203, 38%), BRCA2 (n = 198, 37%), PALB2 (n = 46, 9%), RAD51C (n = 36, 7%), TP53 (n = 16, 3%), and RAD51D (n = 13, 2%). In addition, 35 novel (P/LP) variants, according to our knowledge, were identified, and double mutations in two distinct genes were found in five patients. Interestingly, retesting a subset of BRCA1/2-negative individuals with an expanded panel produced clinically relevant results in 5% of cases. Additionally, combining in silico (splicing impact prediction tools) and in vitro analyses (RT-PCR and Sanger sequencing) highlighted the deleterious impact of four candidate variants on splicing and translation. Our results present an overview of pathogenic variations of HBOC genes in the southeast of France, emphasizing the clinical relevance of cDNA analysis and the importance of retesting BRCA-negative individuals with an expanded panel.
Published: 2023
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99. Association and performance of polygenic risk scores for breast cancer among French women presenting or not a familial predisposition to the disease.

Author: Jiao Y, Truong T, Eon-Marchais S, Mebirouk N, Caputo SM, Dondon MG, Karimi M, Le Gal D, Beauvallet J, Le Floch É, Dandine-Roulland C, Bacq-Daian D, Olaso R, Albuisson J, Audebert-Bellanger S, Berthet P, Bonadona V, Buecher B, Caron O, Cavaillé M, Chiesa J, Colas C, Collonge-Rame MA, Coupier I, Delnatte C, De Pauw A, Dreyfus H, Fert-Ferrer S, Gauthier-Villars M, Gesta P, Giraud S, Gladieff L, Golmard L, Lasset C, Lejeune-Dumoulin S, Léoné M, Limacher JM, Lortholary A, Luporsi É, Mari V, Maugard CM, Mortemousque I, Mouret-Fourme E, Nambot S, Noguès C, Popovici C, Prieur F, Pujol P, Sevenet N, Sobol H, Toulas C, Uhrhammer N, Vaur D, Venat L, Boland-Augé A, Guénel P, Deleuze JF, Stoppa-Lyonnet D, Andrieu N, and Lesueur F
Subjects: Humans, Female, Case-Control Studies, Genetic Predisposition to Disease, Risk Factors, Genes, BRCA2, Breast Neoplasms epidemiology, Breast Neoplasms genetics, Breast Neoplasms pathology
Abstract: Background: Three partially overlapping breast cancer polygenic risk scores (PRS) comprising 77, 179 and 313 SNPs have been proposed for European-ancestry women by the Breast Cancer Association Consortium (BCAC) for improving risk prediction in the general population. However, the effect of these SNPs may vary from one country to another and within a country because of other factors., Objective: To assess their associated risk and predictive performance in French women from (1) the CECILE population-based case-control study, (2) BRCA1 or BRCA2 (BRCA1/2) pathogenic variant (PV) carriers from the GEMO study, and (3) familial breast cancer cases with no BRCA1/2 PV and unrelated controls from the GENESIS study., Results: All three PRS were associated with breast cancer in all studies, with odds ratios per standard deviation varying from 1.7 to 2.0 in CECILE and GENESIS, and hazard ratios varying from 1.1 to 1.4 in GEMO. The predictive performance of PRS 313 in CECILE was similar to that reported in BCAC but lower than that in GENESIS (area under the receiver operating characteristic curve (AUC) = 0.67 and 0.75, respectively). PRS were less performant in BRCA2 and BRCA1 PV carriers (AUC = 0.58 and 0.54 respectively)., Conclusion: Our results are in line with previous validation studies in the general population and in BRCA1/2 PV carriers. Additionally, we showed that PRS may be of clinical utility for women with a strong family history of breast cancer and no BRCA1/2 PV, and for those carrying a predicted PV in a moderate-risk gene like ATM, CHEK2 or PALB2., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DS-L and LG coordinated the genotyping of SNPs included in the PRS of the MammoRisk® test commercialized by Predilife until December 2021. This genotyping was performed in the Department of Genetics of the Institut Curie. All other authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2023
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100. First estimates of diffuse gastric cancer risks for carriers of CTNNA1 germline pathogenic variants.

Author: Coudert M, Drouet Y, Delhomelle H, Svrcek M, Benusiglio PR, Coulet F, Clark DF, Katona BW, van Hest LP, van der Kolk LE, Cats A, van Dieren JM, Nehoray B, Slavin T, Spier I, Hüneburg R, Lobo S, Oliveira C, Boussemart L, Masson L, Chiesa J, Schwartz M, Buecher B, Golmard L, Bouvier AM, Bonadona V, Stoppa-Lyonnet D, Lasset C, and Colas C
Subjects: Humans, Cadherins genetics, Genetic Predisposition to Disease, Heterozygote, Germ Cells pathology, Germ-Line Mutation genetics, alpha Catenin genetics, Stomach Neoplasms epidemiology, Stomach Neoplasms genetics, Stomach Neoplasms pathology
Abstract: Background: Pathogenic variants (PV) of CTNNA1 are found in families fulfilling criteria for hereditary diffuse gastric cancer (HDGC) but no risk estimates were available until now. The aim of this study is to evaluate diffuse gastric cancer (DGC) risks for carriers of germline CTNNA1 PV., Methods: Data from published CTNNA1 families were updated and new families were identified through international collaborations. The cumulative risk of DGC by age for PV carriers was estimated with the genotype restricted likelihood (GRL) method, taking into account non-genotyped individuals and conditioning on all observed phenotypes and genotypes of the index case to obtain unbiased estimates. A non-parametric (NP) and the Weibull functions were used to model the shape of penetrance function with the GRL. Kaplan-Meier incidence curve and standardised incidence ratios were also computed. A 'leave-one-out' strategy was used to evaluate estimate uncertainty., Results: Thirteen families with 46 carriers of PV were included. The cumulative risks of DGC at 80 years for carriers of CTNNA1 PV are 49% and 57%, respectively with the Weibull GRL and NP GRL methods. Risk ratios to population incidence reach particularly high values at early ages and decrease with age. At 40 years, they are equal to 65 and 833, respectively with the Weibull GRL and NP GRL., Conclusion: This is the largest series of CTNNA1 families that provides the first risk estimates of GC. These data will help to improve management and surveillance for these patients and support inclusion of CTNNA1 in germline testing panels., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2022
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