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A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3)

David G Cox12*, Hélène Blanché3, Celeste L Pearce4, Eugenia E Calle5, Graham A Colditz2, Malcolm C Pike4, Demetrius Albanes6, Naomi E Allen7, Pilar Amiano8, Goran Berglund9, Heiner Boeing10, Julie Buring11, Noel Burtt12, Federico Canzian13, Stephen Chanock14, Françoise Clavel-Chapelon15, Heather Spencer Feigelson5, Matthew Freedman167, Christopher A Haiman4, Susan E Hankinson172, Brian E Henderson4, Robert Hoover14, David J Hunter12, Rudolf Kaaks18, Laurence Kolonel19, Peter Kraft12, Loic LeMarchand19, Eiliv Lund20, Domenico Palli21, Petra HM Peeters22, Elio Riboli23, Daniel O Stram4, Michael Thun5, Anne Tjonneland24, Dimitrios Trichopoulos25, Meredith Yeager14 and the Breast and Prostate Cancer Cohort Consortium

Author Affiliations

1 Program in Molecular and Genetic Epidemiology, Epidemiology Department, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA

2 Channing Laboratory, Harvard Medical School, 181 Longwood Ave., Boston, MA, USA

3 CEPH, Fondation Jean Dausset, 27 rue Juliette Dodu, 75010 Paris, France

4 Keck School of Medicine, University of Southern California, East Lake Ave. Los Angeles, CA, 90089 USA

5 Epidemiology and Surveillance Research American Cancer Society, 1599 Clifton Rd. NE, Atlanta, GA, 30329 USA

6 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Executive Blvd Rockville, MD, 20852 USA

7 Cancer Research UK Epidemiology Unit, University of Oxford, Richard Doll Building, Old Road Campus Oxford, UK OX3 7LF

8 Molecular and Nutritional Epidemiology Unit, Scientific Institute of Tuscany, 50131 Florence, Italy

9 Department of Medicine, Lund University, 221 00 Lund, Sweden

10 Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany

11 Division of Preventive Medicine, Brigham & Women's Hospital, Department of Medicine, Harvard Medical School, 900 Commonwealth Ave., Boston, MA 02215, USA

12 Broad Institute at Harvard and the Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, MA 02142, USA

13 Genomic Epidemiology Group, Division of Molecular Genetic Epidemiology, German Cancer Research Center, 69121 Heidelberg, Germany

14 Core Genotyping Facility, National Cancer Institute, 8717 Grovemont Circle, Gaithersburg, MD 20892, USA

15 INSERM, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France

16 Dana-Farber Cancer Institute, Department of Medical Oncology, 44 Binney St., Boston, MA 02115, USA

17 Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave,. Boston, MA 02115, USA

18 Nutrition and Hormones Group, International Agency for Research on Cancer,150 Cours Albert Thomas, 69008 Lyon, France

19 Epidemiology Program, Cancer Research Center, University of Hawaii, 1236 Lauhala St., Honolulu, HI 96813, USA

20 Institute of Community Medicine, University of Tromsø, 9037 Tromsø, Norway

21 Molecular and Nutritional Epidemiology Unit, Scientific Institute of Tuscany, 50131 Florence, Italy

22 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3508 Utrecht, The Netherlands

23 Faculty of Medicine, Division of Epidemiology, Public Health and Primary Care, Imperial College, W2 1PG London, UK

24 Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark

25 Department of Hygiene and Epidemiology, School of Medicine, University of Athens, 75 Mikras Asias Str., 11527 Goudi, Athens, Greece

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Breast Cancer Research 2006, 8:R54  doi:10.1186/bcr1602

Published: 20 September 2006



Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/or androgen receptor (AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3).


The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships (blocks) across the gene were then identified, and haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts (5,603 breast cancer cases and 7,480 controls).


We found no association between any genetic variation (SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed.


Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer.