title: A genome-wide "pleiotropy scan" does not identify new susceptibility loci for estrogen receptor negative breast cancer.
abstract: Approximately 15-30% of all breast cancer tumors are estrogen receptor negative (ER-). Compared with ER-positive (ER+) disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER-negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P<5 × 10(-8)) to perform a secondary analysis of an ER-negative GWAS from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), including 1998 cases and 2305 controls from prospective studies. We then tested the top ten associations (i.e. with the lowest P-values) using three additional populations with a total sample size of 3509 ER+ cases, 2543 ER- cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER-GWAS were significant at the adjusted threshold. 186 variants were associated with ER- breast cancer risk at a conventional threshold of P<0.05, with P-values ranging from 0.049 to 2.3 × 10(-4). None of the variants reached statistical significance in the replication phase. In conclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a "pleiotropic approach".
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Daniele
authors: D
authors: Campa
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Myrto
authors: M
authors: Barrdahl
authors: Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom ; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
authors: Konstantinos K
authors: KK
authors: Tsilidis
authors: Cancer Epidemiology Centre, Cancer Council Victoria, Carlton South, Victoria, Australia ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia.
authors: Gianluca
authors: G
authors: Severi
authors: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America.
authors: W Ryan
authors: WR
authors: Diver
authors: Imperial College, London, United Kingdom.
authors: Afshan
authors: A
authors: Siddiq
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors: Stephen
authors: S
authors: Chanock
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors: Robert N
authors: RN
authors: Hoover
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors: Regina G
authors: RG
authors: Ziegler
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America.
authors: Christine D
authors: CD
authors: Berg
authors: Division of Oncology, Huntsman Cancer Institute at the University of Utah School of Medicine, Salt Lake City, Utah, United States of America.
authors: Saundra S
authors: SS
authors: Buys
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors: Christopher A
authors: CA
authors: Haiman
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors: Brian E
authors: BE
authors: Henderson
authors: Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
authors: Fredrick R
authors: FR
authors: Schumacher
authors: University of Hawaii Cancer Center, Honolulu, Hawaii, United States of America.
authors: Loïc
authors: L
authors: Le Marchand
authors: Department of Cancer Epidemiology/Clinical Cancer Registry, University Cancer Center Hamburg (UCCH), Germany ; Department of Medical Biometrics and Epidemiology, University Medical Center Hamburg-Eppendorf, Germany.
authors: Dieter
authors: D
authors: Flesch-Janys
authors: Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors: Sara
authors: S
authors: Lindström
authors: Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors: David J
authors: DJ
authors: Hunter
authors: Harvard School of Public Health, Boston, Massachusetts, United States of America ; Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America ; Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts, United States of America.
authors: Susan E
authors: SE
authors: Hankinson
authors: Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors: Walter C
authors: WC
authors: Willett
authors: Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors: Peter
authors: P
authors: Kraft
authors: Imperial College, London, United Kingdom ; Université de Lyon, Université Lyon 1, Lyon, France ; Institut National de la Santé et de la Recherche Médicale U1052 Centre de Recherche en Cancérologie de Lyon, Lyon, France ; Centre national de la recherche scientifique UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France ; Centre Léon Bérard, Lyon, France.
authors: David G
authors: DG
authors: Cox
authors: Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, Cambridge, United Kingdom.
authors: Kay-Tee
authors: KT
authors: Khaw
authors: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors: Anne
authors: A
authors: Tjønneland
authors: Institut National de la Santé et de la Recherche Médicale, Centre for research in Epidemiology and Population Health, Nutrition, Hormones and Women's Health team, Villejuif, France ; Université Paris Sud, UMRS 1018, Villejuif, France ; Institut Gustave-Roussy, F-94805, Villejuif, France.
authors: Laure
authors: L
authors: Dossus
authors: Harvard School of Public Health, Boston, Massachusetts, United States of America ; Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece ; Hellenic Health Foundation, Athens, Greece.
authors: Dimitrios
authors: D
authors: Trichopoulos
authors: Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
authors: Salvatore
authors: S
authors: Panico
authors: Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands.
authors: Carla H
authors: CH
authors: van Gils
authors: Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway ; Department of Research, Cancer Registry of Norway, Oslo, Norway ; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden ; Samfundet Folkhälsan, Helsinki, Finland.
authors: Elisabete
authors: E
authors: Weiderpass
authors: Navarre Public Health Institute, Pamplona, Spain ; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Madrid, Spain.
authors: Aurelio
authors: A
authors: Barricarte
authors: Department of Surgery, Umeå University Hospital, Umeå, Sweden.
authors: Malin
authors: M
authors: Sund
authors: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America.
authors: Mia M
authors: MM
authors: Gaudet
authors: Cancer Epidemiology Centre, Cancer Council Victoria, Carlton South, Victoria, Australia ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia.
authors: Graham
authors: G
authors: Giles
authors: Cancer Epidemiology Centre, Cancer Council Victoria, Carlton South, Victoria, Australia ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia.
authors: Melissa
authors: M
authors: Southey
authors: Cancer Epidemiology Centre, Cancer Council Victoria, Carlton South, Victoria, Australia ; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia.
authors: Laura
authors: L
authors: Baglietto
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Jenny
authors: J
authors: Chang-Claude
authors: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Rudolf
authors: R
authors: Kaaks
authors: Genomic Epidemiology Group, German Cancer Research Center, Heidelberg, Germany.
authors: Federico
authors: F
authors: Canzian
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D016208:Databases, Factual; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D012044:Regression Analysis
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha