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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 Cox1,2 email, Hélène Blanché3 email, Celeste L Pearce4 email, Eugenia E Calle5 email, Graham A Colditz2 email, Malcolm C Pike4 email, Demetrius Albanes6 email, Naomi E Allen7 email, Pilar Amiano8 email, Goran Berglund9 email, Heiner Boeing10 email, Julie Buring11 email, Noel Burtt12 email, Federico Canzian13 email, Stephen Chanock14 email, Françoise Clavel-Chapelon15 email, Heather Spencer Feigelson5 email, Matthew Freedman7,16 email, Christopher A Haiman4 email, Susan E Hankinson2,17 email, Brian E Henderson4 email, Robert Hoover14 email, David J Hunter1,2 email, Rudolf Kaaks18 email, Laurence Kolonel19 email, Peter Kraft1,2 email, Loic LeMarchand19 email, Eiliv Lund20 email, Domenico Palli21 email, Petra HM Peeters22 email, Elio Riboli23 email, Daniel O Stram4 email, Michael Thun5 email, Anne Tjonneland24 email, Dimitrios Trichopoulos25 email, Meredith Yeager14 email and the Breast and Prostate Cancer Cohort Consortium

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

author email corresponding author email

Breast Cancer Research 2006, 8:R54doi:10.1186/bcr1602

Published: 20 September 2006

Abstract

Introduction

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).

Methods

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).

Results

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.

Conclusion

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

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