PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1
2017; Impact Journals LLC; Volume: 8; Issue: 61 Linguagem: Inglês
10.18632/oncotarget.21800
ISSN1949-2553
AutoresXiang Jiao, Christos Aravidis, Rajeshwari Marikkannu, Johanna Rantala, Simone Picelli, Tatjana Adamović, Tao Liu, Paula Maguire, Bárbara Kremeyer, Liping Luo, Susanna von Holst, Vinaykumar Kontham, Jessada Thutkawkorapin, Sara Margolin, Quan Du, Johanna Lundin, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang, Joe Dennis, Michael Lush, Christine B. Ambrosone, Irene L. Andrulis, Hoda Anton‐Culver, Natalia Antonenkova, Volker Arndt, Matthias W. Beckmann, Carl Blomqvist, William J. Blot, Bram Boeckx, Stig E. Bojesen, Bernardo Bonanni, Judith S. Brand, Hiltrud Brauch, Hermann Brenner, Annegien Broeks, Thomas Brüning, Barbara Burwinkel, Qiuyin Cai, Jenny Chang‐Claude, Fergus J. Couch, Angela Cox, Simon S. Cross, Sandra Deming-Halverson, Peter Devilee, Isabel dos‐Santos‐Silva, Thilo Dörk, Mikael Eriksson, Peter A. Fasching, Jonine D. Figueroa, Dieter Flesch‐Janys, Henrik Flyger, Marike Gabrielson, Montserrat García‐Closas, Graham G. Giles, Anna González‐Neira, Pascal Guénel, Qi Guo, Melanie Gündert, Christopher A. Haiman, Emily Hallberg, Ute Hamann, Patricia Harrington, Maartje J. Hooning, John L. Hopper, Guanmengqian Huang, Anna Jakubowska, Michael E. Jones, Michael J. Kerin, Veli‐Matti Kosma, Vessela N. Kristensen, Diether Lambrechts, Loı̈c Le Marchand, Jan Lubiński, Graham J. Mann, John W.M. Martens, Thomas Ind, Roger L. Milne, Anna Marie Mulligan, Susan L. Neuhausen, Heli Nevanlinna, Julian Peto, Katri Pylkäs, Paolo Radice, Valerie Rhenius, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Caroline Seynaeve, Mitul Shah, Jacques Simard, Melissa C. Southey, Anthony J. Swerdlow, Thérèse Truong, Camilla Wendt, Robert Winqvist, Wei Zheng, Javier Benı́tez, Alison M. Dunning, Paul D.P. Pharoah, Douglas F. Easton, Kamila Czene, Per Hall, Annika Lindblom,
Tópico(s)BRCA gene mutations in cancer
Resumo// Xiang Jiao 1 , Christos Aravidis 1,2 , Rajeshwari Marikkannu 1 , Johanna Rantala 1 , Simone Picelli 1 , Tatjana Adamovic 1 , Tao Liu 1 , Paula Maguire 1 , Barbara Kremeyer 1 , Liping Luo 1 , Susanna von Holst 1 , Vinaykumar Kontham 1 , Jessada Thutkawkorapin 1 , Sara Margolin 3 , Quan Du 1 , Johanna Lundin 1 , Kyriaki Michailidou 4,5 , Manjeet K. Bolla 4 , Qin Wang 4 , Joe Dennis 4 , Michael Lush 4 , Christine B. Ambrosone 6 , Irene L. Andrulis 7,8 , Hoda Anton-Culver 9 , Natalia N. Antonenkova 10 , Volker Arndt 11 , Matthias W. Beckmann 12 , Carl Blomqvist 13 , William Blot 14,15 , Bram Boeckx 16,17 , Stig E. Bojesen 18,19,20 , Bernardo Bonanni 21 , Judith S. Brand 22 , Hiltrud Brauch 23,24,25 , Hermann Brenner 11,25,26 , Annegien Broeks 27 , Thomas Brüning 28 , Barbara Burwinkel 29,30 , Qiuyin Cai 14 , Jenny Chang-Claude 31,32 , NBCS Collaborators 33,34,35,36,37,38,39,40,41,42,43,44,45,46,47 , Fergus J. Couch 48 , Angela Cox 49 , Simon S. Cross 50 , Sandra L. Deming-Halverson 14 , Peter Devilee 51,52 , Isabel dos-Santos-Silva 53 , Thilo Dörk 54 , Mikael Eriksson 22 , Peter A. Fasching 12,55 , Jonine Figueroa 56,57 , Dieter Flesch-Janys 58,59 , Henrik Flyger 60 , Marike Gabrielson 22 , Montserrat García-Closas 57 , Graham G. Giles 61,62 , Anna González-Neira 63 , Pascal Guénel 64 , Qi Guo 65 , Melanie Gündert 29,30 , Christopher A. Haiman 66 , Emily Hallberg 67 , Ute Hamann 68 , Patricia Harrington 69 , Maartje J. Hooning 70 , John L. Hopper 62 , Guanmengqian Huang 68 , Anna Jakubowska 71 , Michael E. Jones 72 , Michael J. Kerin 73 , Veli-Matti Kosma 74,75,76 , Vessela N. Kristensen 37,41,42 , Diether Lambrechts 16,17 , Loic Le Marchand 77 , Jan Lubinski 71 , Arto Mannermaa 74,75,76 , John W.M. Martens 70 , Alfons Meindl 78 , Roger L. Milne 61,62 , Anna Marie Mulligan 79,80 , Susan L. Neuhausen 81 , Heli Nevanlinna 82 , Julian Peto 53 , Katri Pylkäs 83,84 , Paolo Radice 85 , Valerie Rhenius 69 , Elinor J. Sawyer 86 , Marjanka K. Schmidt 27,87 , Rita K. Schmutzler 88,89,90 , Caroline Seynaeve 70 , Mitul Shah 69 , Jacques Simard 91 , Melissa C. Southey 92 , Anthony J. Swerdlow 72,93 , Thérèse Truong 64 , Camilla Wendt 3 , Robert Winqvist 83,84 , Wei Zheng 14 , kConFab/AOCS Investigators 94,95 , Javier Benitez 63,96 , Alison M. Dunning 69 , Paul D.P. Pharoah 4,69 , Douglas F. Easton 4,69 , Kamila Czene 22 , Per Hall 22 and Annika Lindblom 1 1 Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden 2 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden 3 Department of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden 4 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK 5 Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus 6 Roswell Park Cancer Institute, Buffalo, NY, USA 7 Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada 8 Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada 9 Department of Epidemiology, University of California Irvine, Irvine, CA, USA 10 N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus 11 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany 12 Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany 13 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland 14 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA 15 International Epidemiology Institute, Rockville, MD, USA 16 VIB Center for Cancer Biology, VIB, Leuven, Belgium 17 Laboratory for Translational Genetics, Department of Human Genetics, University of Leuven, Leuven, Belgium 18 Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark 19 Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark 20 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark 21 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy 22 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 23 Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany 24 University of Tübingen, Tübingen, Germany 25 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany 26 Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany 27 Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands 28 Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum, Germany 29 Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany 30 Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany 31 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany 32 Research Group Genetic Cancer Epidemiology, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany 33 Department of Oncology, Haukeland University Hospital, Bergen, Norway 34 Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway 35 Department of Pathology, Akershus University Hospital, Lørenskog, Norway 36 Department of Breast-Endocrine Surgery, Akershus University Hospital, Lørenskog, Norway 37 Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway 38 Department of Breast and Endocrine Surgery, Oslo University Hospital, Ullevål, Oslo, Norway 39 Department of Research, Vestre Viken Hospital, Drammen, Norway 40 Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway 41 Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway 42 Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway 43 National Advisory Unit on Late Effects after Cancer Treatment, Oslo University Hospital Radiumhospitalet, Oslo, Norway 44 Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway 45 Department of Radiology and Nuclear Medicine, Oslo University Hospital Radiumhospitalet, Oslo, Norway 46 Oslo University Hospital, Oslo, Norway 47 Department of Oncology, Oslo University Hospital Ullevål, Oslo, Norway 48 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA 49 Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK 50 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK 51 Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands 52 Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands 53 Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK 54 Gynaecology Research Unit, Hannover Medical School, Hannover, Germany 55 David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, USA 56 Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK 57 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA 58 Institute for Medical Biometrics and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 59 Department of Cancer Epidemiology, Clinical Cancer Registry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany 60 Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark 61 Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, Victoria, Australia 62 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Victoria, Australia 63 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain 64 Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France 65 Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK 66 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA 67 Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA 68 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany 69 Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK 70 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands 71 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland 72 Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK 73 School of Medicine, National University of Ireland, Galway, Ireland 74 Translational Cancer Research Area, University of Eastern Finland, Kuopio, Finland 75 Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland 76 Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland 77 Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA 78 Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany 79 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada 80 Laboratory Medicine Program, University Health Network, Toronto, ON, Canada 81 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA 82 Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland 83 Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland 84 Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland 85 Department of Research, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Milan, Italy 86 Research Oncology, Guy's Hospital, King's College London, London, UK 87 Division of Psychosocial Research and Epidemiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands 88 Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany 89 Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany 90 Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany 91 Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, QC, Canada 92 Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia 93 Division of Breast Cancer Research, The Institute of Cancer Research, London, UK 94 Peter MacCallum Cancer Center, Melbourne, Victoria, Australia 95 The Sir Peter MacCallum Department of Oncology University of Melbourne, Parkville, Australia 96 Centro de Investigación en Red de Enfermedades Raras (CIBERER), Valencia, Spain Correspondence to: Annika Lindblom, email: // Keywords : familial breast cancer, linkage analysis, risk haplotype, sequencing Received : July 06, 2017 Accepted : August 31, 2017 Published : October 12, 2017 Abstract Most non- BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD >2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.
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