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      Is Open Access

      FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium

      1 , 2 , 1 , 3 , 1 , 4 , 5 , 5 , 5 , 3 , 3 , 3 , 6 , 7 , 8 , 9 , 5 , 10 , 11 , 12 , 13 , 14 , 14 , 12 , 15 , 16 , 17 , 17 , kConFab Investigators 18 , Australian Ovarian Cancer Study Group 18 19 , 20 , 21 , 21 , 22 , 23 , 24 , 25 , 26 , 26 , 27 , 28 , 28 , 27 , 28 , 29 , 30 , 30 , 30 , 31 , 32 , 33 , 33 , 32 , 34 , 35 , 36 , 37 , 38 , The GENICA Network 35 36 37 38 39 40 41 , 42 , 42 , 43 , 44 , 43 , 45 , 46 , 43 , 47 , 47 , 47 , 47 , 48 , 49 , 48 , 50 , 48 , 51 , 52 , 51 , 53 , 54 , 55 , 56 , 56 , 57 , 57 , 57 , 57 , 58 , 58 , 58 , 59 , 60 , 60 , 60 , 61 , 62 , 62 , 62 , 62 , 62 , 63 , 64 , 62 , 65 , 66 , 67 , 66 , 68 , 69 , 70 , 71 , 72 , TNBCC 73 , 74 , 75 , 75 , 76 , 76 , 77 , 78 , 77 , 79 , 80 , 81 , 80 , 81 , 80 , 81 , 82 , 83 , 84 , 85 , 84 , 85 , 86 , 87 , 88 , 87 , 88 , 87 , 89 , 90 , 91 , 92 , 91 , 93 , 94 , 90 , 91 , 92 , 90 , 91 , 92 , 95 , 95 , 96 , 96 , 97 , 97 , 97 , 98 , 99 , 71 , 100 , 100 , 100 , 30 , 101 , 30 , 101 , 30 , 101 , 57 , 57 , 57 , 102 , 103 , 103 , 104 , 105 , 106 , 107 , 107 , 108 , 109 , 110 , 111 , 112 , 13 , 113 , 114 , 113 , 115 , 113 , 116 , 116 , 116 , 116 , 112 , 112 , 117 , 118 , 119 , 120 , 120 , 120 , 120 , 121 , 121 , 122 , 123 , 124 , 125 , 124 , 116 , 19 , 3 , 42 , 3 , 42 , 126 , 127 , 1 , 5 , 1 , 30 , 101 , *

      British Journal of Cancer

      Nature Publishing Group

      breast cancer, SNP, FGF receptors, susceptibility, disease subtypes

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background:

          Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium.

          Methods:

          Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.

          Results:

          Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02–1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2.

          Conclusion:

          Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

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          Most cited references 39

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          • Abstract: found
          • Article: not found

          Quantifying heterogeneity in a meta-analysis.

          The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity. Copyright 2002 John Wiley & Sons, Ltd.
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            Haploview: analysis and visualization of LD and haplotype maps.

            Research over the last few years has revealed significant haplotype structure in the human genome. The characterization of these patterns, particularly in the context of medical genetic association studies, is becoming a routine research activity. Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface. http://www.broad.mit.edu/mpg/haploview/ jcbarret@broad.mit.edu
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              • Article: not found

              GenABEL: an R library for genome-wide association analysis.

              Here we describe an R library for genome-wide association (GWA) analysis. It implements effective storage and handling of GWA data, fast procedures for genetic data quality control, testing of association of single nucleotide polymorphisms with binary or quantitative traits, visualization of results and also provides easy interfaces to standard statistical and graphical procedures implemented in base R and special R libraries for genetic analysis. We evaluated GenABEL using one simulated and two real data sets. We conclude that GenABEL enables the analysis of GWA data on desktop computers. http://cran.r-project.org.
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                Author and article information

                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                18 February 2014
                18 February 2014
                : 110
                : 4
                : 1088-1100
                Affiliations
                [1 ]Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO) , Madrid, Spain
                [2 ]Department of Molecular, Cellular and Developmental Biology, Yale University , New Haven, CT, USA
                [3 ]Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge , Cambridge, UK
                [4 ]Biostatistics Unit, IMDEA Food Institute , Madrid, Spain
                [5 ]Human Genotyping-CEGEN Unit, Spanish National Cancer Research Centre (CNIO) , Madrid, Spain
                [6 ]CRUK Cambridge Institute, University of Cambridge , Cambridge, UK
                [7 ]Hospital Monte Naranco , Oviedo, Spain
                [8 ]Department of Pathology, Hospital Universitario La Paz, IdiPAZ (Hospital La Paz Institute for Health Research) Universidad Autonoma de Madrid , Madrid, Spain
                [9 ]Laboratory of Pathology and Oncology, Research Unit, Hospital Universitario La Paz, IdiPAZ , Madrid, Spain
                [10 ]Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm, Sweden
                [11 ]Department of Oncology—Pathology, Karolinska Institutet , Stockholm, Sweden
                [12 ]Division of Genetics and Epidemiology, The Institute of Cancer Research , Sutton, UK
                [13 ]Division of Breast Cancer Research, The Institute of Cancer Research , London, UK
                [14 ]Breakthrough Breast Cancer Research Centre, Division of Breast Cancer Research, The Institute of Cancer Research , London, UK
                [15 ]Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences , Fukuoka, Japan
                [16 ]Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute , Nagoya, Japan
                [17 ]Department of Breast Oncology, Aichi Cancer Center Hospital , Nagoya, Japan
                [18 ]Peter MacCallum Cancer Centre , Melbourne, Victoria, Australia
                [19 ]QIMR Berghofer Institute of Medical Research , Brisbane, Queensland, Australia
                [20 ]Saw Swee Hock School of Public Health, Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System , Singapore, Singapore
                [21 ]Saw Swee Hock School of Public Health, National University of Singapore and National University Health System , Singapore, Singapore
                [22 ]Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System , Singapore, Singapore
                [23 ]Research Oncology, Division of Cancer Studies, Kings College London Guy's Hospital , London, UK
                [24 ]Wellcome Trust Centre for Human Genetics, University of Oxford , Oxford, UK
                [25 ]Oxford Biomedical Research Centre, University of Oxford , Oxford, UK
                [26 ]School of Medicine, Clinical Science Institute, National University of Ireland , Galway, UK
                [27 ]Department of Preventive Medicine, Seoul National University College of Medicine , Seoul, Korea
                [28 ]Department of Biomedical Sciences, Seoul National University Graduate School , Seoul, Korea
                [29 ]Department of Surgery, Seoul National University College of Medicine , Seoul, Korea
                [30 ]Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne , Melbourne, Victoria, Australia
                [31 ]Department of Pathology, University of Melbourne , Melbourne, Victoria, Australia
                [32 ]Cancer Research Initiatives Foundation, Sime Darby Medical Centre , Subang Jaya, Malaysia
                [33 ]Breast Cancer Research Unit, University Malaya Cancer Research Institute, University Malaya Medical Centre , Kuala Lumpur, Malaysia
                [34 ]Singapore Eye Research Institute, National University of Singapore , Singapore
                [35 ]Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology , Stuttgart, Germany
                [36 ]University of Tübingen , Germany
                [37 ]Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA) , Germany
                [38 ]Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg , Germany
                [39 ]Institute for Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf , Germany
                [40 ]Institute of Pathology, Medical Faculty of the University of Bonn , Germany
                [41 ]Department of Internal Medicine, Evangelische Kliniken Bonn GmbH, Johanniter Krankenhaus, Bonn , Germany
                [42 ]Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge , Cambridge, UK
                [43 ]Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital , Toronto, Ontario, Canada
                [44 ]Department of Molecular Genetics, University of Toronto , Toronto, Ontario, Canada
                [45 ]Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto , Toronto, Ontario, Canada
                [46 ]Ontario Cancer Genetics Network, Lunenfeld-Tanenbaum Research Institute , Toronto, Ontario, Canada
                [47 ]Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital , Amsterdam, The Netherlands
                [48 ]Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN , Erlangen, Germany
                [49 ]David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles , CA, USA
                [50 ]Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg , Erlangen, Germany
                [51 ]Institute of Biomedical Sciences, Academia Sinica , Taipei, Taiwan
                [52 ]College of Public Health, China Medical University , Taichong, Taiwan
                [53 ]Tri-Service General Hospital , Taipei, Taiwan
                [54 ]Cancer Center, Kaohsiung Medical University Chung-Ho Memorial Hospital , Kaohsiung, Taiwan
                [55 ]Department of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital , Kaohsiung, Taiwan
                [56 ]Department of Medicine, Vanderbilt University , Nashville, TN USA
                [57 ]Department of Preventive Medicine, Keck School of Medicine, University of Southern California , Los Angeles, CA, USA
                [58 ]CRUK/YCR Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield , Sheffield, UK
                [59 ]Institute of Population Health, University of Manchester , Manchester, UK
                [60 ]Division of Health Sciences, Warwick Medical School , Coventry, UK
                [61 ]Ministry of Public Health , Bangkok, Thailand
                [62 ]Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN, USA
                [63 ]Shanghai Center for Disease Control and Prevention , Shanghai, China
                [64 ]Shanghai Cancer Institute , Shanghai, China
                [65 ]Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT) , Milan, Italy
                [66 ]IFOM, Fondazione Istituto FIRC di Oncologia Molecolare , Milan, Italy
                [67 ]Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori (INT) , Milan, Italy
                [68 ]Cogentech Cancer Genetic Test Laboratory , Milan, Italy
                [69 ]National Cancer Institute , Bangkok, Thailand
                [70 ]Genetic Susceptibility Group, International Agency for Research on Cancer , Lyon, France
                [71 ]Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN, USA
                [72 ]Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University , Columbus, OH, USA
                [73 ]Mayo Clinic , Rochester, MN, USA
                [74 ]Molecular Diagnostics Laboratory, INRASTES, National Centre for Scientific Research "Demokritos" , Athens, Greece
                [75 ]Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research , London, UK
                [76 ]London School of Hygiene and Tropical Medicine , London, UK
                [77 ]Department of Obstetrics and Gynecology, University of Heidelberg , Heidelberg, Germany
                [78 ]National Center for Tumor Diseases, University of Heidelberg , Heidelberg, Germany
                [79 ]Molecular Epidemiology Group, German Cancer Research Center (DKFZ) , Heidelberg, Germany
                [80 ]Inserm (National Institute of Health and Medical Research), CESP (Center for Research in Epidemiology and Population Health), U1018, Environmental Epidemiology of Cancer , Villejuif, France
                [81 ]University Paris-Sud, UMRS 1018 , Villejuif, France
                [82 ]Inserm (National Institute of Health and Medical Research) , U775 Paris, France
                [83 ]Centre de Ressources Biologiques EPIGENETEC , Paris, France
                [84 ]Copenhagen General Population Study, Herlev University Hospital, University of Copenhagen , Copenhagen, Denmark
                [85 ]Department of Clinical Biochemistry, Herlev University Hospital, University of Copenhagen , Copenhagen, Denmark
                [86 ]Department of Breast Surgery, Herlev University Hospital, University of Copenhagen , Copenhagen, Denmark
                [87 ]Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ) , Heidelberg, Germany
                [88 ]German Cancer Consortium (DKTK) , Heidelberg, Germany
                [89 ]Saarland Cancer Registry , Saarbrücken, Germany
                [90 ]School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland , Kuopio, Finland
                [91 ]Biocenter Kuopio, University of Eastern Finland , Kuopio, Finland
                [92 ]Department of Clinical Pathology, Kuopio University Hospital , Kuopio, Finland
                [93 ]School of Medicine, Institute of Clinical Medicine, Oncology, University of Eastern Finland , Kuopio, Finland
                [94 ]Cancer Center, Kuopio University Hospital , Kuopio, Finland
                [95 ]Vesalius Research Center (VRC), VIB , Leuven, Belgium
                [96 ]Multidisciplinary Breast Center, University Hospital Gasthuisberg , Leuven, Belgium
                [97 ]Division of Cancer Epidemiology, German Cancer Research Center (DKFZ) , Heidelberg, Germany
                [98 ]Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf , Hamburg, Germany
                [99 ]Department of Cancer Epidemiology/Clinical Cancer Registry, University Clinic Hamburg-Eppendorf , Hamburg, Germany
                [100 ]Department of Health Sciences Research, Mayo Clinic , Rochester, MN, USA
                [101 ]Cancer Epidemiology Centre, Cancer Council Victoria , Melbourne, Australia
                [102 ]University of Hawaii Cancer Center , Honolulu, HI, USA
                [103 ]Cancer Genomics Laboratory, Centre Hospitalier Universitaire de Quebec Research Center and Laval University , Quebec, Canada
                [104 ]Department of Medicine, McGill University, Montreal , Montreal, Quebec, Canada
                [105 ]Division of Clinical Epidemiology, McGill University Health Centre, Royal Victoria Hospital , Montreal, Quebec, Canada
                [106 ]Département de médecine sociale et préventive, Département de santé environnementale et santé au travail, Université de Montréal , Montreal, Quebec, Canada
                [107 ]Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, Oulu University Hospital , Oulu, Finland
                [108 ]Department of Oncology, Oulu University Hospital, University of Oulu , Oulu, Finland
                [109 ]Department of Surgery, Oulu University Hospital, University of Oulu , Oulu, Finland
                [110 ]Department of Human Genetics, Leiden University Medical Center , Leiden, The Netherlands
                [111 ]Department of Surgical Oncology, Leiden University Medical Center , Leiden, The Netherlands
                [112 ]Department of Medical Oncology, Family Cancer Clinic, Erasmus University Medical Centre , Rotterdam, The Netherlands
                [113 ]Division of Cancer Epidemiology and Genetics, National Cancer Institute , Rockville, MD, USA
                [114 ]Division of Genetics and Epidemiology, Institute of Cancer Research and Breakthrough Breast Cancer Research Centre , London, UK
                [115 ]Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Memorial Cancer Center & Institute of Oncology , Warsaw, Poland
                [116 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm, Sweden
                [117 ]Department of Clinical Genetics, Family Cancer Clinic, Erasmus University Medical Center , Rotterdam, The Netherlands
                [118 ]Department of Surgical Oncology, Family Cancer Clinic, Erasmus University Medical Centre , Rotterdam, The Netherlands
                [119 ]Human Genetics Division, Genome Institute of Singapore , Singapore, Singapore
                [120 ]Department of Genetics and Pathology, Pomeranian Medical University , Szczecin, Poland
                [121 ]Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital , Helsinki, Finland
                [122 ]Department of Clinical Genetics, Helsinki University Central Hospital , Helsinki, Finland
                [123 ]Department of Oncology, Helsinki University Central Hospital , Helsinki, Finland
                [124 ]Department of Obstetrics and Gynaecology, Hannover Medical School , Hannover, Germany
                [125 ]Department of Radiation Oncology, Hannover Medical School , Hannover, Germany
                [126 ]Servicio de Cirugía General y Especialidades, Hospital Monte Naranco , Oviedo, Spain
                [127 ]Servicio de Oncología Médica, Hospital Universitario La Paz , Madrid, Spain
                bjc2013769
                10.1038/bjc.2013.769
                3929867
                24548884
                Copyright © 2014 Cancer Research UK

                From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

                Categories
                Genetics and Genomics

                Oncology & Radiotherapy

                fgf receptors, snp, breast cancer, disease subtypes, susceptibility

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