Androgen receptor CAG repeat polymorphism and risk of TMPRSS2:ERG positive prostate cancer
Menée aux Etats-Unis auprès de 291 cas et 1 221 témoins, cette étude évalue l'association entre un polymorphisme du récepteur des androgènes et le risque de cancer de la prostate en fonction du statut du gène de fusion TMPRSS2-ERG
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 percent of tumors of prostate cancer patients. 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. Odds ratios (ORs) and 95% confidence intervals (CIs) 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.