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

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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.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

    Bhupinder Bharaj, Andreas Scorilas, Eleftherios P. Diamandis, Michael A. Levesque & Barry R. Hoffman

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

    Bhupinder Bharaj, Andreas Scorilas, Eleftherios P. Diamandis, Michael A. Levesque & Barry R. Hoffman

  3. Department of Gynecologic Oncology, Institute of Obstetrics and Gynecology, University of Turin, Turin, Italy

    Maurizia Giai

  4. Toronto-Sunnybrook Regional Cancer Centre, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada

    Donald J.A. Sutherland

  5. Department of Medicine, University of Toronto, Toronto, Ontario, Canada

    Donald J.A. Sutherland

Authors
  1. Bhupinder Bharaj
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  2. Andreas Scorilas
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  3. Eleftherios P. Diamandis
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  4. Maurizia Giai
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  5. Michael A. Levesque
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  6. Donald J.A. Sutherland
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  7. Barry R. Hoffman
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Bharaj, B., Scorilas, A., Diamandis, E.P. et al. Breast cancer prognostic significance of a single nucleotide polymorphism in the proximal androgen response element of the prostate specific antigen gene promoter. Breast Cancer Res Treat 61, 111–119 (2000). https://doi.org/10.1023/A:1006459613498

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