Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs).

Autor: Darabi H; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Beesley J; Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia., Droit A; Département de Médecine Moléculaire, Faculté de Médecine, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada., Kar S; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Nord S; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway., Moradi Marjaneh M; Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia., Soucy P; Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada., Michailidou K; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.; Department of Electron Microscopy/Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus., Ghoussaini M; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Fues Wahl H; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Bolla MK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Wang Q; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Dennis J; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Alonso MR; Human Genotyping-CEGEN Unit, Human Cancer Genetic Program, Spanish National Cancer Research Centre, Madrid, Spain., Andrulis IL; Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, Canada., Anton-Culver H; Department of Epidemiology, University of California Irvine, Irvine, CA, USA., Arndt V; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany., Beckmann MW; Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany., Benitez J; Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain.; Centro de Investigación en Red de Enfermedades Raras, Valencia, Spain., Bogdanova NV; Department of Radiation Oncology, Hannover Medical School, Hannover, Germany., Bojesen SE; Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Brauch H; Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.; University of Tübingen, Tübingen, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany., Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany., Broeks A; Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands., Brüning T; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum, Germany., Burwinkel B; Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.; Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany., Chang-Claude J; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.; University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Choi JY; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.; Cancer Research Institute, Seoul National University, Seoul, Korea., Conroy DM; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Couch FJ; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Cox A; Sheffield Cancer Research, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK., Cross SS; Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK., Czene K; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Devilee P; Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands., Dörk T; Gynaecology Research Unit, Hannover Medical School, Hannover, Germany., Easton DF; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Fasching PA; Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.; David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, CA, USA., Figueroa J; Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Medical School, Edinburgh, UK.; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Fletcher O; Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.; Division of Breast Cancer Research, The Institute of Cancer Research, London, UK., Flyger H; Department of Breast Surgery, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark., Galle E; Vesalius Research Center, Leuven, Belgium.; Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium., García-Closas M; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA., Giles GG; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia., Goldberg MS; Department of Medicine, McGill University, Montreal, Canada.; Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montreal, Canada., González-Neira A; Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain., Guénel P; Cancer &Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France., Haiman CA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Hallberg E; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Hamann U; Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany., Hartman M; Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.; Department of Surgery, National University Health System, Singapore, Singapore., Hollestelle A; Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Hopper JL; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia., Ito H; Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan., Jakubowska A; Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland., Johnson N; Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK.; Division of Breast Cancer Research, The Institute of Cancer Research, London, UK., Kang D; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.; Cancer Research Institute, Seoul National University, Seoul, Korea.; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea., Khan S; Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland., Kosma VM; Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.; Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.; Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland., Kriege M; Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Kristensen V; Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.; K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.; Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, Oslo, Norway., Lambrechts D; Vesalius Research Center, Leuven, Belgium.; Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium., Le Marchand L; University of Hawaii Cancer Center, Honolulu, HI, USA., Lee SC; Department of Hematology-Oncology, National University Health System, Singapore, Singapore.; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Lindblom A; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Lophatananon A; Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK., Lubinski J; Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland., Mannermaa A; Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.; Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Kuopio, Finland.; Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland., Manoukian S; Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT), Milan, Italy., Margolin S; Department of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden., Matsuo K; Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Japan., Mayes R; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., McKay J; International Agency for Research on Cancer, Lyon, France., Meindl A; Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany., Milne RL; Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia., Muir K; Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.; Institute of Population Health, University of Manchester, Manchester, UK., Neuhausen SL; Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA., Nevanlinna H; Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland., Olswold C; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Orr N; Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK., Peterlongo P; IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, Milan, Italy., Pita G; Human Genotyping-CEGEN Unit, Human Cancer Genetic Program, Spanish National Cancer Research Centre, Madrid, Spain., Pylkäs K; Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland.; Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland., Rudolph A; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Sangrajrang S; National Cancer Institute, Bangkok, Thailand., Sawyer EJ; Research Oncology, Guy's Hospital, King's College London, London, UK., Schmidt MK; Netherlands Cancer Institute, Antoni van Leeuwenhoek hospital, Amsterdam, The Netherlands., Schmutzler RK; Center for Hereditary Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany.; Center for Integrated Oncology (CIO), University Hospital of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany., Seynaeve C; Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Shah M; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK., Shen CY; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.; Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Shu XO; Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Southey MC; Department of Pathology, The University of Melbourne, Melbourne, Australia., Stram DO; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Surowy H; Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.; Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany., Swerdlow A; Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Teo SH; Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia.; Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia., Tessier DC; McGill University and Génome Québec Innovation Centre, Montréal, Canada., Tomlinson I; Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK., Torres D; Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Institute of Human Genetics, Pontificia Universidad Javeriana, Bogota, Colombia., Truong T; Cancer &Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif, France., Vachon CM; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA., Vincent D; McGill University and Génome Québec Innovation Centre, Montréal, Canada., Winqvist R; Laboratory of Cancer Genetics and Tumor Biology, Cancer and Translational Medicine Research Unit, Biocenter Oulu, University of Oulu, Oulu, Finland.; Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre Oulu, Oulu, Finland., Wu AH; Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Wu PE; Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan., Yip CH; Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia., Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA., Pharoah PD; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Hall P; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Edwards SL; Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia., Simard J; Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada., French JD; Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia., Chenevix-Trench G; Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia., Dunning AM; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2016 Sep 07; Vol. 6, pp. 32512. Date of Electronic Publication: 2016 Sep 07.
DOI: 10.1038/srep32512
Abstrakt: Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10(-09), r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10(-11), r(2) = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.
Databáze: MEDLINE