Research article

The androgen receptor CAG repeat polymorphism and modification of breast cancer risk in BRCA1 and BRCA2 mutation carriers

Amanda B Spurdle¹ , Antonis C Antoniou² , David L Duffy¹ , Nirmala Pandeya¹ , Livia Kelemen¹ , Xiaoqing Chen¹ , Susan Peock² , Margaret R Cook² , Paula L Smith² , David M Purdie¹ , Beth Newman³ , Gillian S Dite⁴ , Carmel Apicella⁴ , Melissa C Southey⁴ , Graham G Giles⁵ , John L Hopper⁴ , kConFaB, EMBRACE Study Collaborators, ABCFS, AJBCS, Georgia Chenevix-Trench¹ and Douglas F Easton²

¹  Queensland Institute of Medical Research, Brisbane, Australia

²  Cancer Research UK Genetic Epidemiology Unit, University of Cambridge, Cambridge, UK

³  School of Public Health, Queensland University of Technology, Brisbane, Australia

⁴  University of Melbourne, Melbourne, Australia

⁵  The Cancer Council Victoria, Carlton, Australia

author email corresponding author email

Breast Cancer Res 2005, 7:R176-R183doi:10.1186/bcr971

Published:	16 December 2004

Abstract

Introduction

The androgen receptor (AR) gene exon 1 CAG repeat polymorphism encodes a string of 9–32 glutamines. Women with germline BRCA1 mutations who carry at least one AR allele with 28 or more repeats have been reported to have an earlier age at onset of breast cancer.

Methods

A total of 604 living female Australian and British BRCA1 and/or BRCA2 mutation carriers from 376 families were genotyped for the AR CAG repeat polymorphism. The association between AR genotype and disease risk was assessed using Cox regression. AR genotype was analyzed as a dichotomous covariate using cut-points previously reported to be associated with increased risk among BRCA1 mutation carriers, and as a continuous variable considering smaller allele, larger allele and average allele size.

Results

There was no evidence that the AR CAG repeat polymorphism modified disease risk in the 376 BRCA1 or 219 BRCA2 mutation carriers screened successfully. The rate ratio associated with possession of at least one allele with 28 or more CAG repeats was 0.74 (95% confidence interval 0.42–1.29; P = 0.3) for BRCA1 carriers, and 1.12 (95% confidence interval 0.55–2.25; P = 0.8) for BRCA2 carriers.

Conclusion

The AR exon 1 CAG repeat polymorphism does not appear to have an effect on breast cancer risk in BRCA1 or BRCA2 mutation carriers.