Dataset Information
Androgen receptor CAG repeat polymorphism and risk of TMPRSS2:ERG-positive prostate cancer.
Ontology highlight
ABSTRACT: 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.
SUBMITTER: Yoo S
PROVIDER: S-EPMC4184923 | biostudies-literature | 2014 Oct
REPOSITORIES: biostudies-literature
Publications
Androgen receptor CAG repeat polymorphism and risk of TMPRSS2:ERG-positive prostate cancer.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20140612 10
<h4>Background</h4>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.<h4>Methods</h4>We undertook a nested case-control study to investigat ...[more]