Role ofp73Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance

[摘要] Background. Molecular markers for prostate cancer (PCa) risks are currently lacking. Here we address the potential association of a dinucleotide polymorphism (DNP) in exon 2 of thep73gene with PCa risk/progression and discern any disruption of p73 protein isoforms levels in cells harboring ap73DNP allele.Methods. We investigated the association betweenp73DNP genotype and PCa risk/aggressiveness and survival by fitting logistic regression models in 1,292 incident cases and 682 controls.Results. Although we detected no association betweenp73DNP and PCa risk, a significant inverse relationship betweenp73DNP and PCa aggressiveness (AT/AT + GC/AT versus GC/GC, OR = 0.55, 95%Cl = 0.31–0.99) was detected. Also,p73DNP is marginally associated with overall death (dominant model, HR = 0.76, 95%Cl = 0.57–1.00,P=0.053) as well as PCa specific death (HR = 0.69, 95%Cl = 0.45–1.06,P=0.09). Western blot analyses for p73 protein isoforms indicate that cells heterozygous for thep73DNP have lower levels of ∆Np73 relative to TAp73 (P<0.001).Conclusions. Our findings are consistent with an association betweenp73DNP and low risk for PCa aggressiveness by increasing the expressed TAp73/∆Np73 protein isoform ratio.

[学科分类] 肿瘤学