Abstract for presentation at 11th International Congress of Human Genetics

SRD5A2 A49T and V89L gene polymorphisms, prostate cancer, serum androgen levels and androgenetic alopecia

  • Vanessa Hayes, Garvan Institute of Medical Research, Australia
  • Gianluca Severi, The Cancer Council of Victoria, Australia
  • Howard Morris, Hanson Institute, Australia
  • Wayne Tilley, Hanson Institute, Australia
  • Dallas English, The Cancer Council of Victoria, Australia
  • Robert Sutherland, Garvan Institute of Medial Research, Australia
  • John Hopper, University of Melbourne, Australia
  • Graham Giles, The Cancer Council of Victoria, Australia

    • Testosterone is converted to active dihydrotestosterone (DHT) via the enzyme 5 alpha-reductase type 2 (SRD5A2). Thus the SRD5A2 gene has been implicated in prostate cancer and male patterned balding. While DHT levels are increased in the balding scalp, two SRD5A2 polymorphisms, A49T and V89L, have been associated with prostate cancer risk. The aim of this study was to examine the effect of these well-defined polymorphisms on prostate cancer risk, survival, clinicopathological behaviour, serum androgen levels and androgenetic alopecia. Subjects were participants in a large Australian population- and age-matched case-control study of prostate cancer. Serum hormone levels of controls were determined and genotyping performed using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry for 827 cases and 736 controls. No association between the V89L polymorphism and prostate cancer phenotypes, androgen levels and alopecia were found. Carriers of the rarer A49T A allele were at a higher risk of prostate cancer (P = 0.02) and at about 50% lower risk of balding (cases and controls P = 0.04, controls P = 0.001) compared to men homozygous for the more common G allele. While we found little evidence of association between this variant and circulating levels of testosterone, dehydroepiandrosterone sulfate, androstenedione, sex hormone-binding globulin, and estradiol, levels of circulating androstanediol glucuronide (AG) were significantly lower in A49T A allele carriers (P < 0.0001). Our study provides strong evidence that the A49T, but not the V89L variant, in the SRD5A2 gene is functional and modulates AG circulating levels. The same variant appears to be associated with increased prostate cancer risk and decreased risk of baldness.

    Conference Organiser - ICMS Pty Ltd