Research article
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)
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* Corresponding author: David G Cox dcox@hsph.harvard.edu
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
Breast Cancer Research 2006, 8:R54 doi:10.1186/bcr1602
Published: 20 September 2006Abstract
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.