Androgen Receptor Cag Repeat Polymorphism and Risk of Tmprss2:erg Positive Prostate Cancer
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CitationYoo, S., A. Pettersson, K. M. Jordahl, R. T. Lis, S. Lindstrom, A. Meisner, E. J. Nuttall, et al. 2014. “Androgen Receptor CAG Repeat Polymorphism and Risk of TMPRSS2:ERG-Positive Prostate Cancer.” Cancer Epidemiology Biomarkers & Prevention 23 (10): 2027–31. https://doi.org/10.1158/1055-9965.epi-14-0020.
AbstractBackground: 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.
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