Breast Cancer Research and Treatment

, Volume 59, Issue 2, pp 153–161

Shorter CAG repeat length in the androgen receptor gene is associated with more aggressive forms of breast cancer

Authors

  • He Yu
    • Department of MedicineLouisiana State University Medical Centre
  • Bhupinder Bharaj
    • Department of Pathology and Laboratory MedicineMount Sinai Hospital
  • Evyenia J.K. Vassilikos
    • Department of Pathology and Laboratory MedicineMount Sinai Hospital
  • Maurizia Giai
    • Department of Gynecologic Oncology, Institute of Obstetrics/GynecologyUniversity of Turin
  • Eleftherios P. Diamandis
    • Department of Pathology and Laboratory MedicineMount Sinai Hospital
    • Department of Laboratory Medicine and Pathobiology, Banting InstituteUniversity of Toronto
Article

DOI: 10.1023/A:1006356502820

Cite this article as:
Yu, H., Bharaj, B., Vassilikos, E.J. et al. Breast Cancer Res Treat (2000) 59: 153. doi:10.1023/A:1006356502820

Abstract

The androgen receptor (AR) is a transcription factor mediating the action of androgens. The AR gene is localized on chromosome X and it contains a series of CAG trinucleotide repeats. The length of the CAG repeats varies among individuals and this polymorphism is believed to be related to AR transcriptional activity. Studies have shown that fewer CAG repeats are associated with an increased risk as well as more aggressive forms of prostate cancer. Although AR is expressed in breast cancer and the impact of androgen and AR on breast cancer has been recognized, the role of the CAG repeats in breast cancer remains unknown. In this study, we measured the CAG repeats in breast cancer tissue using a PCR-based method. Of the 133 patients with primary breast cancer, 102 were heterozygous and 31 were homozygous. The mean CAG repeat number for homozygous women was 21; for heterozygous women the repeat number mean was 20 for the short allele and 24 for the long allele. The length of CAG repeats either in one allele or in both alleles was inversely correlated with the histological grade of breast cancer (r = −0.23 or −0.26, respectively, p<0.05). An association between positive lymph nodes and fewer CAG repeats in both alleles was also suggested (p = 0.06). Furthermore, survival analysis indicated that the total number of CAG repeats in both alleles was associated with patient overall survival. With every CAG repeat increase, there was a 6% reduction in the risk of death (RR = 0.94, p = 0.03). The association remained significant after controlling for the homozygous and heterozygous status (RR = 0.92, p = 0.01). The association became no longer significant when clinical and pathological variables were adjusted in the analysis but this could be due to the reduction of sample size in the multivariate analysis. CAG heterozygosity and difference in number of CAG repeats between the two alleles were not associated with either disease features or patient survival. Our results suggest that longer CAG repeats may occur more frequently in less aggressive cancer and that the CAG repeats may play a role in breast cancer progression.

breast cancer prognosisprognostic markersandrogen receptor polymorphismsCAG repeatspolyglutamine repeats
Download to read the full article text

Copyright information

© Kluwer Academic Publishers 2000