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Nat Commun. 2014 Oct 24;5:5303. doi: 10.1038/ncomms6303.

Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk.

Author information

  • 11] Program in Genetic Epidemiology and Statistical Genetics, Harvard School Of Public Health, Boston, Massachusetts 02115, USA [2] Department of Epidemiology, Harvard School Of Public Health, Boston, Massachusetts 02115, USA.
  • 21] Centre for Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK [2] Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • 3Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
  • 4Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.
  • 5Hormonal and Reproductive Epidemiology Branch, National Cancer Institute, Bethesda, Maryland 20850, USA.
  • 6Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • 7Centre for Genetic Origins of Health and Disease, University of Western Australia, Perth, Western Australia 6009, Australia.
  • 8Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
  • 9Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
  • 101] Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid 28029, Spain [2] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiología y Salud Pública-CIBERESP), Madrid 28029, Spain.
  • 111] Centre for Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK [2] Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK [3] Plastic Surgery Unit, Royal Free Hospital, London NW3 2QG, UK.
  • 12Centre for Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK.
  • 13Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB1 8RN, UK.
  • 141] Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB1 8RN, UK [2] The Icahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, The Mindich Child Health and Development Institute, New York, New York 10029, USA.
  • 15Division of Cardiovascular Disease, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • 16Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • 171] Department of Gynecology and Obstetrics, Erlangen University Hospital, Friedrich Alexander University of Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, 910 54 Erlangen, Germany [2] Division Hematology/Oncology, Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, California 90024, USA.
  • 181] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia [2] Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
  • 19Department of Pathology, University of Melbourne, Melbourne, Victoria 3010, Australia.
  • 20Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
  • 21Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
  • 221] Program in Genetic Epidemiology and Statistical Genetics, Harvard School Of Public Health, Boston, Massachusetts 02115, USA [2] Department of Epidemiology, Harvard School Of Public Health, Boston, Massachusetts 02115, USA [3] Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
  • 231] Program in Genetic Epidemiology and Statistical Genetics, Harvard School Of Public Health, Boston, Massachusetts 02115, USA [2] Department of Epidemiology, Harvard School Of Public Health, Boston, Massachusetts 02115, USA [3] Department of Biostatistics, Harvard School Of Public Health, Boston, Massachusetts 02115, USA.
  • 241] Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA [2] Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • 25Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
  • 261] Centre for Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK [2] Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK [3] Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
  • 27Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9.

Abstract

Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5 × 10(-8)) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B and SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23 and TMEM184B). Four of these regions are known breast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (P<0.05) in a large meta-analysis. These results provide further evidence of a shared genetic basis between mammographic density and breast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease-susceptibility loci.

PMID:
25342443
[PubMed - indexed for MEDLINE]
PMCID:
PMC4320806
Free PMC Article

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