Androgen receptor CAG repeat polymorphism and risk of TMPRSS2:ERG-positive prostate cancer

Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):2027-31. doi: 10.1158/1055-9965.EPI-14-0020. Epub 2014 Jun 12.


Background: The androgen receptor (AR) is an essential gene in prostate cancer pathogenesis and progression. Genetic variation in AR exists, including a polymorphic CAG repeat sequence that is inversely associated with transcriptional activity. Experimental data suggest that heightened AR activity facilitates formation of TMPRSS2:ERG, a gene fusion present in approximately 50% of tumors of patients with prostate cancer.

Methods: We undertook a nested case-control study to investigate the hypothesis that shorter CAG repeat length would be associated with prostate cancer risk defined by TMPRSS2:ERG status. The study included 291 men with prostate cancer (147 ERG-positive) and 1,221 cancer-free controls. ORs and 95% confidence intervals (CI) were calculated using logistic regression.

Results: Median CAG repeat length (interquartile range) among controls was 22 (20-24). Men with shorter CAG repeats had an increased risk of ERG-positive (OR, 1.07 per 1 repeat decrease; 95% CI, 1.00-1.14), but not ERG-negative prostate cancer (OR, 0.99 per 1 repeat decrease; 95% CI, 0.93-1.05).

Conclusions: These data suggest that shorter CAG repeats are specifically associated with development of TMPRSS2:ERG-positive prostate cancer.

Impact: Our results provide supportive evidence that androgen signaling underlies the development of prostate tumors that harbor TMPRSS2:ERG. Moreover, these results suggest that TMPRSS2:ERG may represent a unique molecular subtype of prostate cancer with an etiology distinct from TMPRSS2:ERG-negative disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Prostatic Neoplasms / genetics*
  • Receptors, Androgen / genetics*
  • Trinucleotide Repeats


  • AR protein, human
  • Oncogene Proteins, Fusion
  • Receptors, Androgen
  • TMPRSS2-ERG fusion protein, human