Tags

Type your tag names separated by a space and hit enter

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

Abstract

BACKGROUND

Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk.

METHOD

We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation.

RESULTS

Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05.

CONCLUSION

This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.

Links

  • PMC Free PDF
  • PMC Free Full Text
  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA.

    ,

    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA.

    ,

    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    ,

    Proteomics Center, CHU de Québec Research Center and Department of Molecular Medicine, Laval University, Quebec, Canada.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, CB1 8RN, UK.

    ,

    Department of Surgery, St Vincent's Hospital, Melbourne, VIC, Australia.

    ,

    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia.

    ,

    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    ,

    Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Padua, Italy.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

    ,

    Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

    ,

    Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Canada.

    ,

    Department of Epidemiology, University of California Irvine, Irvine, CA, USA.

    ,

    N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.

    ,

    Department of Pathology, Landspitali University Hospital and BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

    ,

    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    ,

    University of Texas MD Anderson Cancer Center, Houston, TX, USA.

    ,

    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.

    ,

    McGill University and Génome Québec Innovation Centre, Montréal, Canada.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

    ,

    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA.

    ,

    Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain. Centro de Investigación en Red de Enfermedades Raras, Valencia, Spain.

    ,

    Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia.

    ,

    Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

    ,

    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA. International Epidemiology Institute, Rockville, MD, USA.

    ,

    Department of Radiation Oncology, Hannover Medical School, Hannover, Germany.

    ,

    Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

    ,

    Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan, Italy.

    ,

    Department of 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 Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    ,

    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.

    ,

    International Agency for Research on Cancer, Lyon, France.

    ,

    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), Heidelberg, Germany.

    ,

    Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

    ,

    Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum, Bochum, Germany.

    ,

    Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany. Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    ,

    Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.

    ,

    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA.

    ,

    Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain.

    ,

    Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia.

    ,

    Australian Breast Cancer Tissue Bank, Westmead Millennium Institute, University of Sydney, Sydney, Australia.

    ,

    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

    ,

    Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea. Cancer Research Institute, Seoul National University, Seoul, South Korea.

    ,

    Center for Medical Genetics, Ghent University, Ghent, Belgium.

    ,

    Westmead Millenium Institute for Medical Research, University of Sydney, Sydney, Australia.

    ,

    Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield, UK.

    ,

    Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield, UK.

    ,

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    ,

    Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA, USA.

    ,

    Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Madrid, Spain.

    ,

    Center for Medical Genetics, Ghent University, Ghent, Belgium.

    ,

    Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

    ,

    Oncogenetics Group, University Hospital Vall d'Hebron, Vall d'Hebron Institute of Oncology (VHIO) and Universitat Autònoma de Barcelona, Barcelona, Spain.

    ,

    Department of Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

    ,

    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

    ,

    Department of Genetics, University of Pretoria, Pretoria, South Africa.

    ,

    Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.

    ,

    Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

    ,

    Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada.

    ,

    Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, UK.

    ,

    Institute of Human Genetics, Muenster, Germany.

    ,

    Division of Population Sciences, Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

    ,

    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    ,

    Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.

    ,

    Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    ,

    Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

    , ,

    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.

    ,

    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

    ,

    Department of Breast Surgery, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.

    ,

    ANZ GOTG Coordinating Centre, Australia New Zealand GOG, Camperdown, NSW, Australia.

    ,

    Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel.

    ,

    Section of Genetic Oncology, Deparment of Laboratory Medicine, University and University Hospital of Pisa, Pisa, Italy.

    ,

    Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.

    ,

    Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, MA, USA.

    ,

    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.

    ,

    Institute of Human Genetics, University Würzburg, Wurzburg, Germany.

    ,

    INSERM U1052, CNRS UMR5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, Lyon, France.

    ,

    Genetic Epidemiology of Cancer team, Inserm, U900, Institut Curie, Mines ParisTech, 75248, Paris, France.

    ,

    INSERM U1052, CNRS UMR5286, Université Lyon, Centre de Recherche en Cancérologie de Lyon, Lyon, France.

    ,

    Department of Tumour Biology, Institut Curie, Paris, France. Institut Curie, INSERM U830, Paris, France. Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

    , ,

    Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global health, The University of Melbourne, Melbourne, Australia. Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.

    ,

    Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.

    ,

    Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.

    ,

    Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid, Spain.

    ,

    Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.

    ,

    Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France. University Paris-Sud, Villejuif, France.

    ,

    Department of Gynaecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen, Germany.

    ,

    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

    ,

    Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

    ,

    Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    ,

    Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

    ,

    Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

    ,

    Cancer Center, Kuopio University Hospital, 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.

    ,

    Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore. Department of Surgery, National University Health System, Singapore, Singapore.

    ,

    Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia. Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.

    ,

    Cancer Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

    ,

    Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands.

    ,

    Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands.

    , ,

    Suburban Hospital, Bethesda, MD, USA. Care of City of Hope Clinical Cancer Genetics Community Research Network, Duarte, CA, USA.

    ,

    Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.

    ,

    Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

    ,

    Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL, USA.

    ,

    Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA, USA. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.

    ,

    N.N. Petrov Institute of Oncology, St. Petersburg, Russia.

    ,

    Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.

    ,

    Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi, Japan.

    ,

    Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

    ,

    State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania.

    ,

    Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

    ,

    Department of Clinical Genetics, Aarhus University Hospital, Aarhus, N, Denmark.

    ,

    Department of Epidemiology, Cancer Prevention Institute of California, Fremont, CA, USA. Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, CA, USA. Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.

    ,

    Genomics Center, Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec City, QC, Canada.

    ,

    Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.

    ,

    Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    ,

    Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea. Cancer Research Institute, Seoul National University, Seoul, South Korea.

    ,

    Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

    ,

    Department of Pathology, Oulu University Hospital, University of Oulu, Oulu, Finland.

    ,

    School of Medicine, National University of Ireland, Galway, Ireland.

    ,

    Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

    ,

    Institute of Biochemistry and Genetics, Ufa Scientific Center of Russian Academy of Sciences, Ufa, Russia. Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russia.

    ,

    Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada. Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.

    ,

    Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research "Demokritos", Athens, Greece.

    ,

    Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, MA, USA. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.

    ,

    The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China. Department of Surgery, The University of Hong Kong, Hong Kong, China.

    ,

    Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer, Israel.

    ,

    Vesalius Research Center, Leuven, Belgium. Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.

    ,

    Molecular Diagnostic Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, Barcelona, Spain.

    ,

    University of Hawaii Cancer Center, Honolulu, HI, USA.

    ,

    Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

    ,

    Department of Surgery, Soonchunhyang University and Hospital, Seoul, South Korea.

    ,

    Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

    ,

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    ,

    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.

    ,

    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

    ,

    Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK.

    ,

    Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

    ,

    Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD, USA.

    ,

    Cancer Center, Kuopio University Hospital, 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.

    ,

    Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), Milan, Italy.

    ,

    Department of Oncology - Pathology, Karolinska Institutet, Stockholm, Sweden.

    ,

    Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany. National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany.

    ,

    Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka, Japan.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    ,

    Division of Gynaecology and Obstetrics, Technische Universität München, Munich, Germany.

    ,

    Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, Villejuif, France. University Paris-Sud, Villejuif, France.

    ,

    Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), Padua, Italy.

    ,

    Division of Health Sciences, Warwick Medical School, Warwick University, Coventry, UK. Institute of Population Health, University of Manchester, Manchester, UK.

    ,

    Laboratory Medicine Program, University Health Network, Toronto, ON, Canada. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

    ,

    Department of Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

    ,

    Beckman Research Institute of City of Hope, Duarte, CA, USA.

    ,

    Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

    ,

    Carbone Cancer Center, University of Wisconsin, Madison, WI, USA. Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

    ,

    Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo, Norway.

    ,

    Department of Medicine and Genetics, University of California, San Francisco, San Francisco, CA, USA.

    ,

    Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

    ,

    Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.

    ,

    Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, IL, USA.

    ,

    Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

    ,

    Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), Madrid, Spain. Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.

    ,

    Unit of Medical Genetics, Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.

    ,

    Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.

    ,

    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

    ,

    University Hospital Gashuisberg, Leuven, Belgium.

    ,

    Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), Milan, Italy.

    ,

    IFOM, Fondazione Istituto FIRC (Italian Foundation of Cancer Research) di Oncologia Molecolare, Milan, Italy.

    ,

    Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

    ,

    Department of Obstetrics and Gynecology, and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

    ,

    Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.

    ,

    Department of Biomedical Sciences, Faculty of Science and Technology, University of Westminster, London, UK.

    ,

    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 Tumori (INT), Milan, Italy.

    ,

    Section of Cancer Genetics, The Institute of Cancer Research, London, UK.

    ,

    Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA.

    ,

    Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. Department of Basic Sciences, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH & RC), Lahore, Pakistan.

    ,

    Clalit National Israeli Cancer Control Center and Department of Community Medicine and Epidemiology, Carmel Medical Center and B. Rappaport Faculty of Medicine, Haifa, Israel.

    ,

    Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, Cologne, Germany.

    ,

    Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

    ,

    Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, USA.

    ,

    National Cancer Institute, Bangkok, Thailand.

    ,

    Research Oncology, Guy's Hospital, King's College London, London, UK.

    ,

    Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

    ,

    Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, Cologne, Germany. Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, Cologne, Germany. Center for Integrated Oncology, University Hospital of Cologne, Cologne, Germany. Center for Molecular Medicine, University Hospital of Cologne, Cologne, Germany.

    ,

    Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.

    ,

    Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.

    ,

    Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

    ,

    School of Public Health, China Medical University, Taichung, Taiwan. Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

    ,

    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA.

    ,

    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA.

    ,

    Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

    ,

    Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.

    ,

    Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

    ,

    Centre Hospitalier Universitaire de Québec Research Center and Laval University, Quebec City, QC, Canada.

    ,

    Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Parkville, VIC, Australia.

    ,

    Hannover Medical School, Hannover, Germany.

    ,

    Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.

    ,

    National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.

    ,

    Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON, Canada.

    ,

    Department of Genetics, Portuguese Oncology Institute, Porto, Portugal. Biomedical Sciences Institute (ICBAS), Porto University, Porto, Portugal.

    ,

    Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia. Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, Kuala Lumpur, Malaysia.

    ,

    Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.

    ,

    McGill University and Génome Québec Innovation Centre, Montréal, Canada.

    ,

    Genetic Counseling Unit, Hereditary Cancer Program, IDIBELL (Bellvitge Biomedical Research Institute), Catalan Institute of Oncology, Barcelona, Spain.

    ,

    Department of Clinical Genetics, Odense University Hospital, Odense, C, Denmark.

    ,

    Latvian Biomedical Research and Study Centre, Riga, Latvia.

    ,

    Program in Cancer Genetics, Departments of Human Genetics and Oncology, McGill University, Montreal, QC, Canada. Currently at Medical School Cambridge University, Cambridge, UK.

    ,

    Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.

    ,

    Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.

    ,

    Section of Cancer Genetics, The Institute of Cancer Research, London, UK.

    ,

    Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.

    ,

    Department of Genetics, University of Pretoria, Pretoria, South Africa.

    ,

    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

    ,

    Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

    ,

    Department of Obstetrics and Gynecology, University of Ulm, Ulm, Germany.

    ,

    Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte, CA, USA.

    ,

    Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford, CA, USA. Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.

    ,

    Laboratory of Cancer Genetics and Tumor Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, Oulu, Finland. Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland.

    ,

    Singapore Eye Research Institute, National University of Singapore, Singapore, Singapore.

    ,

    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

    ,

    Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.

    ,

    Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

    ,

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    ,

    Department of Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia. Peter MacCallum Cancer Center, The University of Melbourne, Melbourne, Australia.

    , , ,

    Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

    ,

    Genomics Center, Centre Hospitalier Universitaire de Québec Research Center, Laval University, Québec City, Canada.

    ,

    Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    ,

    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

    Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, 2525 West End Avenue, 8th Floor, Nashville, TN, 37203-1738, USA. wei.zheng@vanderbilt.edu.

    Source

    Breast cancer research : BCR 18:1 2016 06 21 pg 64

    MeSH

    Alleles
    BRCA1 Protein
    Breast Neoplasms
    Case-Control Studies
    Chromosome Mapping
    Chromosomes, Human, Pair 12
    Computational Biology
    Databases, Genetic
    Enhancer Elements, Genetic
    Epigenesis, Genetic
    European Continental Ancestry Group
    Female
    Genetic Predisposition to Disease
    Genome-Wide Association Study
    Genotype
    Haplotypes
    Heterozygote
    Humans
    Mutation
    Odds Ratio
    Polymorphism, Single Nucleotide
    Population Surveillance
    Promoter Regions, Genetic
    Quantitative Trait Loci
    Risk

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    27459855

    Citation

    Zeng, Chenjie, et al. "Identification of Independent Association Signals and Putative Functional Variants for Breast Cancer Risk Through Fine-scale Mapping of the 12p11 Locus." Breast Cancer Research : BCR, vol. 18, no. 1, 2016, p. 64.
    Zeng C, Guo X, Long J, et al. Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. Breast Cancer Res. 2016;18(1):64.
    Zeng, C., Guo, X., Long, J., Kuchenbaecker, K. B., Droit, A., Michailidou, K., ... Zheng, W. (2016). Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. Breast Cancer Research : BCR, 18(1), p. 64. doi:10.1186/s13058-016-0718-0.
    Zeng C, et al. Identification of Independent Association Signals and Putative Functional Variants for Breast Cancer Risk Through Fine-scale Mapping of the 12p11 Locus. Breast Cancer Res. 2016 06 21;18(1):64. PubMed PMID: 27459855.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus. AU - Zeng,Chenjie, AU - Guo,Xingyi, AU - Long,Jirong, AU - Kuchenbaecker,Karoline B, AU - Droit,Arnaud, AU - Michailidou,Kyriaki, AU - Ghoussaini,Maya, AU - Kar,Siddhartha, AU - Freeman,Adam, AU - Hopper,John L, AU - Milne,Roger L, AU - Bolla,Manjeet K, AU - Wang,Qin, AU - Dennis,Joe, AU - Agata,Simona, AU - Ahmed,Shahana, AU - Aittomäki,Kristiina, AU - Andrulis,Irene L, AU - Anton-Culver,Hoda, AU - Antonenkova,Natalia N, AU - Arason,Adalgeir, AU - Arndt,Volker, AU - Arun,Banu K, AU - Arver,Brita, AU - Bacot,Francois, AU - Barrowdale,Daniel, AU - Baynes,Caroline, AU - Beeghly-Fadiel,Alicia, AU - Benitez,Javier, AU - Bermisheva,Marina, AU - Blomqvist,Carl, AU - Blot,William J, AU - Bogdanova,Natalia V, AU - Bojesen,Stig E, AU - Bonanni,Bernardo, AU - Borresen-Dale,Anne-Lise, AU - Brand,Judith S, AU - Brauch,Hiltrud, AU - Brennan,Paul, AU - Brenner,Hermann, AU - Broeks,Annegien, AU - Brüning,Thomas, AU - Burwinkel,Barbara, AU - Buys,Saundra S, AU - Cai,Qiuyin, AU - Caldes,Trinidad, AU - Campbell,Ian, AU - Carpenter,Jane, AU - Chang-Claude,Jenny, AU - Choi,Ji-Yeob, AU - Claes,Kathleen B M, AU - Clarke,Christine, AU - Cox,Angela, AU - Cross,Simon S, AU - Czene,Kamila, AU - Daly,Mary B, AU - de la Hoya,Miguel, AU - De Leeneer,Kim, AU - Devilee,Peter, AU - Diez,Orland, AU - Domchek,Susan M, AU - Doody,Michele, AU - Dorfling,Cecilia M, AU - Dörk,Thilo, AU - Dos-Santos-Silva,Isabel, AU - Dumont,Martine, AU - Dwek,Miriam, AU - Dworniczak,Bernd, AU - Egan,Kathleen, AU - Eilber,Ursula, AU - Einbeigi,Zakaria, AU - Ejlertsen,Bent, AU - Ellis,Steve, AU - Frost,Debra, AU - Lalloo,Fiona, AU - ,, AU - Fasching,Peter A, AU - Figueroa,Jonine, AU - Flyger,Henrik, AU - Friedlander,Michael, AU - Friedman,Eitan, AU - Gambino,Gaetana, AU - Gao,Yu-Tang, AU - Garber,Judy, AU - García-Closas,Montserrat, AU - Gehrig,Andrea, AU - Damiola,Francesca, AU - Lesueur,Fabienne, AU - Mazoyer,Sylvie, AU - Stoppa-Lyonnet,Dominique, AU - ,, AU - Giles,Graham G, AU - Godwin,Andrew K, AU - Goldgar,David E, AU - González-Neira,Anna, AU - Greene,Mark H, AU - Guénel,Pascal, AU - Haeberle,Lothar, AU - Haiman,Christopher A, AU - Hallberg,Emily, AU - Hamann,Ute, AU - Hansen,Thomas V O, AU - Hart,Steven, AU - Hartikainen,Jaana M, AU - Hartman,Mikael, AU - Hassan,Norhashimah, AU - Healey,Sue, AU - Hogervorst,Frans B L, AU - Verhoef,Senno, AU - ,, AU - Hendricks,Carolyn B, AU - Hillemanns,Peter, AU - Hollestelle,Antoinette, AU - Hulick,Peter J, AU - Hunter,David J, AU - Imyanitov,Evgeny N, AU - Isaacs,Claudine, AU - Ito,Hidemi, AU - Jakubowska,Anna, AU - Janavicius,Ramunas, AU - Jaworska-Bieniek,Katarzyna, AU - Jensen,Uffe Birk, AU - John,Esther M, AU - Joly Beauparlant,Charles, AU - Jones,Michael, AU - Kabisch,Maria, AU - Kang,Daehee, AU - Karlan,Beth Y, AU - Kauppila,Saila, AU - Kerin,Michael J, AU - Khan,Sofia, AU - Khusnutdinova,Elza, AU - Knight,Julia A, AU - Konstantopoulou,Irene, AU - Kraft,Peter, AU - Kwong,Ava, AU - Laitman,Yael, AU - Lambrechts,Diether, AU - Lazaro,Conxi, AU - Le Marchand,Loic, AU - Lee,Chuen Neng, AU - Lee,Min Hyuk, AU - Lester,Jenny, AU - Li,Jingmei, AU - Liljegren,Annelie, AU - Lindblom,Annika, AU - Lophatananon,Artitaya, AU - Lubinski,Jan, AU - Mai,Phuong L, AU - Mannermaa,Arto, AU - Manoukian,Siranoush, AU - Margolin,Sara, AU - Marme,Frederik, AU - Matsuo,Keitaro, AU - McGuffog,Lesley, AU - Meindl,Alfons, AU - Menegaux,Florence, AU - Montagna,Marco, AU - Muir,Kenneth, AU - Mulligan,Anna Marie, AU - Nathanson,Katherine L, AU - Neuhausen,Susan L, AU - Nevanlinna,Heli, AU - Newcomb,Polly A, AU - Nord,Silje, AU - Nussbaum,Robert L, AU - Offit,Kenneth, AU - Olah,Edith, AU - Olopade,Olufunmilayo I, AU - Olswold,Curtis, AU - Osorio,Ana, AU - Papi,Laura, AU - Park-Simon,Tjoung-Won, AU - Paulsson-Karlsson,Ylva, AU - Peeters,Stephanie, AU - Peissel,Bernard, AU - Peterlongo,Paolo, AU - Peto,Julian, AU - Pfeiler,Georg, AU - Phelan,Catherine M, AU - Presneau,Nadege, AU - Radice,Paolo, AU - Rahman,Nazneen, AU - Ramus,Susan J, AU - Rashid,Muhammad Usman, AU - Rennert,Gad, AU - Rhiem,Kerstin, AU - Rudolph,Anja, AU - Salani,Ritu, AU - Sangrajrang,Suleeporn, AU - Sawyer,Elinor J, AU - Schmidt,Marjanka K, AU - Schmutzler,Rita K, AU - Schoemaker,Minouk J, AU - Schürmann,Peter, AU - Seynaeve,Caroline, AU - Shen,Chen-Yang, AU - Shrubsole,Martha J, AU - Shu,Xiao-Ou, AU - Sigurdson,Alice, AU - Singer,Christian F, AU - Slager,Susan, AU - Soucy,Penny, AU - Southey,Melissa, AU - Steinemann,Doris, AU - Swerdlow,Anthony, AU - Szabo,Csilla I, AU - Tchatchou,Sandrine, AU - Teixeira,Manuel R, AU - Teo,Soo H, AU - Terry,Mary Beth, AU - Tessier,Daniel C, AU - Teulé,Alex, AU - Thomassen,Mads, AU - Tihomirova,Laima, AU - Tischkowitz,Marc, AU - Toland,Amanda E, AU - Tung,Nadine, AU - Turnbull,Clare, AU - van den Ouweland,Ans M W, AU - van Rensburg,Elizabeth J, AU - Ven den Berg,David, AU - Vijai,Joseph, AU - Wang-Gohrke,Shan, AU - Weitzel,Jeffrey N, AU - Whittemore,Alice S, AU - Winqvist,Robert, AU - Wong,Tien Y, AU - Wu,Anna H, AU - Yannoukakos,Drakoulis, AU - Yu,Jyh-Cherng, AU - Pharoah,Paul D P, AU - Hall,Per, AU - Chenevix-Trench,Georgia, AU - ,, AU - ,, AU - Dunning,Alison M, AU - Simard,Jacques, AU - Couch,Fergus J, AU - Antoniou,Antonis C, AU - Easton,Douglas F, AU - Zheng,Wei, Y1 - 2016/06/21/ PY - 2015/12/23/received PY - 2016/05/18/accepted PY - 2016/7/28/entrez PY - 2016/7/28/pubmed PY - 2017/8/8/medline KW - BRAC1 mutation carriers KW - Breast cancer KW - CCDC91 KW - Fine-scale mapping KW - Genetic risk factor KW - PTHLH SP - 64 EP - 64 JF - Breast cancer research : BCR JO - Breast Cancer Res. VL - 18 IS - 1 N2 - BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk. SN - 1465-542X UR - https://www.unboundmedicine.com/medline/citation/27459855/Identification_of_independent_association_signals_and_putative_functional_variants_for_breast_cancer_risk_through_fine_scale_mapping_of_the_12p11_locus_ L2 - https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-016-0718-0 DB - PRIME DP - Unbound Medicine ER -