Cancer Genetics

You have full text access to this OnlineOpen article

5α-Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia

  1. Vanessa M. Hayes1,2,†,‡,*,
  2. Gianluca Severi3,4,†,
  3. Emma J.D. Padilla1,
  4. Howard A. Morris5,
  5. Wayne D. Tilley5,6,
  6. Melissa C. Southey7,8,
  7. Dallas R. English3,4,
  8. Robert L. Sutherland1,2,
  9. John L. Hopper4,
  10. Peter Boyle8,
  11. Graham G. Giles3,4

Article first published online: 29 NOV 2006

DOI: 10.1002/ijc.22408

Issue

International Journal of Cancer

International Journal of Cancer

Volume 120, Issue 4, pages 776–780, 15 February 2007

Additional Information

How to Cite

Hayes, V. M., Severi, G., Padilla, E. J.D., Morris, H. A., Tilley, W. D., Southey, M. C., English, D. R., Sutherland, R. L., Hopper, J. L., Boyle, P. and Giles, G. G. (2007), 5α-Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia. Int. J. Cancer, 120: 776–780. doi: 10.1002/ijc.22408

Author Information

  1. 1

    Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia

  2. 2

    University of New South Wales, Sydney, Australia

  3. 3

    Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia

  4. 4

    Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne, Melbourne, Australia

  5. 5

    Hanson Institute, Adelaide, Australia

  6. 6

    Dame Roma Mitchell Cancer Research Laboratories, University of Adelaide, Adelaide, Australia

  7. 7

    Department of Pathology, University of Melbourne, Melbourne, Australia

  8. 8

    International Agency for Research on Cancer, Lyon, France

  1. †

    These authors contributed equally to the manuscript.

  2. ‡

    Fax: +61-2-92958321.

*Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia

  1. †

    These authors contributed equally to the manuscript.

  2. ‡

    Fax: +61-2-92958321.

Publication History

  1. Issue published online: 27 DEC 2006
  2. Article first published online: 29 NOV 2006
  3. Manuscript Accepted: 12 SEP 2006
  4. Manuscript Received: 1 AUG 2006

Funded by

  • National Health and Medical Research Council. Grant Numbers: 251533, 940394, 991129, 299955, 396407
  • Cancer Institute of New South Wales
  • Tattersall Family Foundation
  • Whitten Foundation
  • Armati Family Foundation, Australia
  • BNP Paribas Foundation, Australia and France
  • Infrastructure was provided by the Australian Cancer Research Foundation Unit for the Molecular Genetics of Cancer
  • The Cancer Council Victoria

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (101K)

Keywords:

  • SRD5A2;
  • polymorphisms;
  • prostate cancer risk;
  • population-based case-control study;
  • plasma androgens;
  • androgenetic alopecia

Abstract

Controversy exists over the significance of associations between the SRD5A2 (5α-reductase type 2) polymorphisms, A49T and V89L, and risk of prostate cancer. These potentially functional polymorphisms may alter life-long exposure to androgens with subsequent effects on male health and aging. The aim of this study was to examine the association of these variants with prostate cancer risk, plasma hormone levels and androgenetic alopecia. Subjects include 827 cases and 736 controls from an Australian population-based case–control study of prostate cancer. Information on prostate cancer risk factors and patterns of balding were collected. Plasma levels of testosterone, 3α-diol glucuronide (3α-diolG), dehydroepiandrosterone sulfate, androstenedione, sex hormone-binding globulin and estradiol were measured for controls. No associations with the V89L polymorphism were found. Carriers of the rarer A49T A allele were at a 60% higher risk of prostate cancer (OR = 1.60; 95% CI 1.09–2.36; p = 0.02) and 50% lower risk of vertex and frontal balding (p = 0.03) compared with men homozygous for the more common G allele. Although we found little evidence of association between this variant and plasma levels of 5 measured androgens, circulating 3α-diolG levels were 34% lower in A49T A allele carriers (p < 0.0001). Our study provides evidence that the SRD5A2 A49T A variant is associated with an increased risk of prostate cancer, lower levels of circulating 3α-diolG and decreased risk of baldness. These findings raise important questions with respect to previous assumptions concerning hormonal influences on prostate cancer risk in ageing males. © 2006 Wiley-Liss, Inc.

View Full Article (HTML) Get PDF (101K)