A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer

Christopher A Haiman; Gary K Chen; Celine M Vachon; Federico Canzian; Alison Dunning; Robert C Millikan; Xianshu Wang; Foluso Ademuyiwa; Shahana Ahmed; Christine B Ambrosone; Laura Baglietto; Rosemary Balleine; Elisa V Bandera; Matthias W Beckmann; Christine D Berg; Leslie Bernstein; Carl Blomqvist; William J Blot; Hiltrud Brauch; Julie E Buring; Lisa A Carey; Jane E Carpenter; Jenny Chang-Claude; Stephen J Chanock; Daniel I Chasman; Christine L Clarke; Angela Cox; Simon S Cross; Sandra L Deming; Robert B Diasio; Athanasios M Dimopoulos; W Ryan Driver; Thomas Dünnebier; Lorraine Durcan; Diana Eccles; Christopher K Edlund; Arif B Ekici; Peter A Fasching; Heather S Feigelson; Dieter Flesch-Janys; Florentia Fostira; Asta Försti; George Fountzilas; Susan M Gerty; Graham G Giles; Andrew K Godwin; Paul Goodfellow; Nikki Graham; Dario Greco; Ute Hamann; Susan E Hankinson; Arndt Hartmann; Rebecca Hein; Judith Heinz; Andrea Holbrook; Robert N Hoover; Jennifer J Hu; David J Hunter; Sue A Ingles; Astrid Irwanto; Jennifer Ivanovich; Esther M John; Nicola Johnson; Arja Jukkola-Vuorinen; Rudolf Kaaks; Yon-Dschun Ko; Laurence N Kolonel; Irene Konstantopoulou; Veli-Matti Kosma; Swati Kulkarni; Diether Lambrechts; Adam M Lee; Loïc Le Marchand; Timothy Lesnick; Jianjun Liu; Sara Lindstrom; Arto Mannermaa; Sara Margolin; Nicholas G Martin; Penelope Miron; Grant W Montgomery; Heli Nevanlinna; Stephan Nickels; Sarah Nyante; Curtis Olswold; Julie Palmer; Harsh Pathak; Dimitrios Pectasides; Charles M Perou; Julian Peto; Paul D P Pharoah; Loreall C Pooler; Michael F Press; Katri Pylkäs; Timothy R Rebbeck; Jorge L Rodriguez-Gil; Lynn Rosenberg; Eric Ross; Thomas Rüdiger; Isabel dos Santos Silva; Elinor Sawyer; Marjanka K Schmidt; Rüdiger Schulz-Wendtland; Fredrick Schumacher; Gianluca Severi; Xin Sheng; Lisa B Signorello; Hans-Peter Sinn; Kristen N Stevens; Melissa C Southey; William J Tapper; Ian Tomlinson; Frans B L Hogervorst; Els Wauters; JoEllen Weaver; Hans Wildiers; Robert Winqvist; David Van Den Berg; Peggy Wan; Lucy Y Xia; Drakoulis Yannoukakos; Wei Zheng; Regina G Ziegler; Afshan Siddiq; Susan L Slager; Daniel O Stram; Douglas Easton; Peter Kraft; Brian E Henderson; Gene Environm Interaction Breast C; Fergus J Couch

doi:10.1038/ng.985

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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer

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A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer

Christopher A Haiman, Gary K Chen, Celine M Vachon, Federico Canzian, Alison Dunning, Robert C Millikan, Xianshu Wang, Foluso Ademuyiwa, Shahana Ahmed, Christine B Ambrosone, …

Nature genetics, Vol.43(12), pp.1210-1214

12/01/2011

DOI: https://doi.org/10.1038/ng.985

PMCID: PMC3279120

PMID: 22037553

Abstract

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10 −10 ). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10 −9 ), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10 −9 ). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.

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Title: A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor–negative breast cancer
Creators: Christopher A Haiman - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Gary K Chen - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Celine M Vachon - Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
Federico Canzian - Genomic Epidemiology Group, DKFZ, Heidelberg, Germany
Alison Dunning - Centre for Cancer Genetic Epidemiology, Strangeways Laboratory, Worts Causeway, Cambridge, UK
Robert C Millikan - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
Xianshu Wang - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
Foluso Ademuyiwa - Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA
Shahana Ahmed - Centre for Cancer Genetic Epidemiology, Strangeways Laboratory, Worts Causeway, Cambridge, UK
Christine B Ambrosone - Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York, USA
Laura Baglietto - Cancer Epidemiology Centre, The Cancer Council Victoria & Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Victoria, Australia
Rosemary Balleine - Department of Translational Oncology, Westmead Hospital, Western Sydney Local Health Network, Westmead, New South Wales, Australia
Elisa V Bandera - The Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
Matthias W Beckmann - Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
Christine D Berg - Division of Cancer Prevention, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA
Leslie Bernstein - Division of Cancer Etiology, Department of Population Science, Beckman Research Institute, City of Hope, California, USA
Carl Blomqvist - Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
William J Blot - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Hiltrud Brauch - Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany
Julie E Buring - Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Lisa A Carey - Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
Jane E Carpenter - Australian Breast Cancer Tissue Bank, University of Sydney at the Westmead Millennium Institute, Westmead, New South Wales, Australia
Jenny Chang-Claude - Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
Stephen J Chanock - Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA
Daniel I Chasman - Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Christine L Clarke - Australian Breast Cancer Tissue Bank, University of Sydney at the Westmead Millennium Institute, Westmead, New South Wales, Australia
Angela Cox - Institute for Cancer Studies, Department of Oncology, Faculty of Medicine, Dentistry & Health, University of Sheffield, Sheffield, UK
Simon S Cross - Academic Unit of Pathology, Department of Neuroscience, Faculty of Medicine, Dentistry & Health, University of Sheffield, Sheffield, UK
Sandra L Deming - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Robert B Diasio - Department of Pharmacology, Mayo Clinic, Rochester, Minnesota, USA
Athanasios M Dimopoulos - Department of Clinical Therapeutics, “Alexandra” Hospital, University of Athens School of Medicine, Athens, Greece
W Ryan Driver - Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, USA
Thomas Dünnebier - Molecular Genetics of Breast Cancer, DKFZ, Heidelberg, Germany
Lorraine Durcan - Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
Diana Eccles - Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
Christopher K Edlund - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Arif B Ekici - Institute of Human Genetics, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany
Peter A Fasching - Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
Heather S Feigelson - Kaiser Permanente Colorado, Denver, Colorado, USA
Dieter Flesch-Janys - Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany
Florentia Fostira - Molecular Diagnostics Laboratory Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research “Demokritos”, Athens, Greece
Asta Försti - Division of Molecular Genetic Epidemiology, DKFZ, Heidelberg, Germany
George Fountzilas - Department of Medical Oncology, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece
Susan M Gerty - Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
Graham G Giles - Cancer Epidemiology Centre, The Cancer Council Victoria & Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Victoria, Australia
Andrew K Godwin - Department of Pathology and Laboratory Medicine, Kansas University Medical Center, Lawrence, Kansas, USA
Paul Goodfellow - Washington University School of Medicine, Barnes-Jewish Hospital and Siteman Cancer Center, St. Louis, Missouri, USA
Nikki Graham - Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
Dario Greco - Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
Ute Hamann - Molecular Genetics of Breast Cancer, DKFZ, Heidelberg, Germany
Susan E Hankinson - Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
Arndt Hartmann - Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany
Rebecca Hein - Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
Judith Heinz - Institute for Medical Biometrics and Epidemiology, University Clinic Hamburg-Eppendorf, Hamburg, Germany
Andrea Holbrook - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Robert N Hoover - Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA
Jennifer J Hu - Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida, USA
David J Hunter - Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
Sue A Ingles - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Astrid Irwanto - Human Genetics Division, Genome Institute of Singapore, Singapore
Jennifer Ivanovich - Washington University School of Medicine, Barnes-Jewish Hospital and Siteman Cancer Center, St. Louis, Missouri, USA
Esther M John - Cancer Prevention Institute of California, Fremont, California
Nicola Johnson - Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK
Arja Jukkola-Vuorinen - Department of Oncology, Oulu University Hospital, University of Oulu, Oulu, Finland
Rudolf Kaaks - Division of Cancer Epidemiology, DKFZ, Heidelberg, Germany
Yon-Dschun Ko - Department of Internal Medicine, Evangelische Kliniken Johanniter- und Waldkrankenhaus Bonn gGmbH, Bonn, Germany
Laurence N Kolonel - Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, Hawaii, USA
Irene Konstantopoulou - Molecular Diagnostics Laboratory Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research “Demokritos”, Athens, Greece
Veli-Matti Kosma - Department of Pathology, Imaging Centre, Kuopio University Hospital, Kuopio, Finland
Swati Kulkarni - Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York, USA
Diether Lambrechts - Vesalius Research Center, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
Adam M Lee - Department of Pharmacology, Mayo Clinic, Rochester, Minnesota, USA
Loïc Le Marchand - Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, Hawaii, USA
Timothy Lesnick - Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
Jianjun Liu - Human Genetics Division, Genome Institute of Singapore, Singapore
Sara Lindstrom - Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
Arto Mannermaa - Institute of Clinical Medicine, Department of Pathology, University of Eastern Finland Biocenter Kuopio, Kuopio, Finland
Sara Margolin - Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
Nicholas G Martin - Queensland Institute of Medical Research (QIMR) Genome-Wide Association Study Collective, Brisbane, Queensland, Australia
Penelope Miron - Dana-Farber Cancer Institute, Boston, Massachusetts, USA
Grant W Montgomery - Queensland Institute of Medical Research (QIMR) Genome-Wide Association Study Collective, Brisbane, Queensland, Australia
Heli Nevanlinna - Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
Stephan Nickels - Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
Sarah Nyante - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA
Curtis Olswold - Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
Julie Palmer - Slone Epidemiology Center at Boston University, Boston, Massachusetts, USA
Harsh Pathak - Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
Dimitrios Pectasides - Department of Internal Medicine, Oncology Section, “Hippokration” Hospital, Athens, Greece
Charles M Perou - Departments of Genetics and Pathology, Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, North Carolina, USA
Julian Peto - Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
Paul D P Pharoah - Centre for Cancer Genetic Epidemiology, Strangeways Laboratory, Worts Causeway, Cambridge, UK
Loreall C Pooler - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Michael F Press - Department of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
Katri Pylkäs - Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, Oulu, Finland
Timothy R Rebbeck - University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
Jorge L Rodriguez-Gil - Sylvester Comprehensive Cancer Center and Department of Epidemiology and Public Health, University of Miami Miller School of Medicine, Miami, Florida, USA
Lynn Rosenberg - Slone Epidemiology Center at Boston University, Boston, Massachusetts, USA
Eric Ross - Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
Thomas Rüdiger - Institute of Pathology, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany
Isabel dos Santos Silva - Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
Elinor Sawyer - National Institute for Health Research Comprehensive Biomedical Research Centre, Guy’s & St. Thomas’ National Health Service Foundation Trust, London, UK
Marjanka K Schmidt - Division of Experimental Therapy and Molecular Pathology and Division of Epidemiology, Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Rüdiger Schulz-Wendtland - Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany
Fredrick Schumacher - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Gianluca Severi - Cancer Epidemiology Centre, The Cancer Council Victoria & Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Victoria, Australia
Xin Sheng - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Lisa B Signorello - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Hans-Peter Sinn - Department of Pathology, University Hospital Heidelberg, Heidelberg, Germany
Kristen N Stevens - Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
Melissa C Southey - Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia
William J Tapper - Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
Ian Tomlinson - Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK
Frans B L Hogervorst - Family Cancer Clinic, Netherlands Cancer Institut–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Els Wauters - Vesalius Research Center, Vlaams Instituut voor Biotechnologie, Leuven, Belgium
JoEllen Weaver - Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA
Hans Wildiers - Multidisciplinary Breast Center, University Hospital Gasthuisberg, Leuven, Belgium
Robert Winqvist - Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, Oulu, Finland
David Van Den Berg - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Peggy Wan - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Lucy Y Xia - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Drakoulis Yannoukakos - Molecular Diagnostics Laboratory Institute of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research “Demokritos”, Athens, Greece
Wei Zheng - Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Regina G Ziegler - Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA
Afshan Siddiq - Imperial College, London, UK
Susan L Slager - Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
Daniel O Stram - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Douglas Easton - Centre for Cancer Genetic Epidemiology, Strangeways Laboratory, Worts Causeway, Cambridge, UK
Peter Kraft - Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
Brian E Henderson - Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
Gene Environm Interaction Breast C
Fergus J Couch - Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
Publication Details: Nature genetics, Vol.43(12), pp.1210-1214
Date published: 12/01/2011
Grant note: R01 CA128978-04 || CA / National Cancer Institute : NCI R01 CA122340-04 || CA / National Cancer Institute : NCI
Academic Unit: Cancer Epidemiology and Health Outcomes
Language: English
Resource Type: Journal article
Identifiers: 991031665966504646