Breast Cancer Research and Treatment

, Volume 61, Issue 2, pp 111–119

Breast cancer prognostic significance of a single nucleotide polymorphism in the proximal androgen response element of the prostate specific antigen gene promoter

  • Bhupinder Bharaj
  • Andreas Scorilas
  • Eleftherios P. Diamandis
  • Maurizia Giai
  • Michael A. Levesque
  • Donald J.A. Sutherland
  • Barry R. Hoffman
Article

Abstract

Prostate Specific Antigen (PSA) expression by breast epithelial cells is associated with favorable breast cancer prognosis. In preliminary studies, we found that a nucleotide variation (G → A) at position −158 in the androgen response element (ARE-1) of the PSA promoter was present in four out of 9 breast tumors examined and in a breast carcinoma cell line. We have now determined the nucleotide composition at position −158 of DNA extracted from 148 well-characterized breast tumors and compared tumor genotype with that of controls without cancer, with tumor PSA concentration and with clinicopathological variables, overall survival and disease free survival. The G → A base change at position −158 is a polymorphism. Allelotypes were similarly distributed in breast cancer patients and controls. The Mann–Whitney U Test showed a significantly higher tumor PSA concentration in tumors that presented a homozygous G as opposed to homozygous A genotype. Genotype at position −158 was not associated with clinicopathological variables in contingency table analysis. Univariate Cox regression models showed a 28% reduction in risk for death in patients with homozygous G genotype compared to those with homozygous A genotype (P=0.03). However, ARE-I genotype did not significantly add to the prognostic power in the multivariate model of overall survival. In summary, the base change at position −158 is a polymorphism that may affect breast cancer prognosis, but further studies are required to confirm this possibility and to investigate the relevance of this polymorphism in terms of breast cancer susceptibility.

androgen receptor breast cancer mutation polymorphism prognosis 

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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Bhupinder Bharaj
    • 1
    • 2
  • Andreas Scorilas
    • 1
    • 2
  • Eleftherios P. Diamandis
    • 1
    • 2
  • Maurizia Giai
    • 3
  • Michael A. Levesque
    • 1
    • 2
  • Donald J.A. Sutherland
    • 4
    • 5
  • Barry R. Hoffman
    • 1
    • 2
  1. 1.Department of Pathology and Laboratory MedicineMount Sinai HospitalTorontoCanada
  2. 2.Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada
  3. 3.Department of Gynecologic Oncology, Institute of Obstetrics and GynecologyUniversity of TurinTurinItaly
  4. 4.Toronto-Sunnybrook Regional Cancer CentreSunnybrook and Women's College Health Sciences CentreTorontoCanada
  5. 5.Department of MedicineUniversity of TorontoTorontoCanada

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