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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 the  p73  gene with PCa risk/progression and discern any disruption of p73 protein isoforms levels in cells harboring a  p73  DNP allele.  Methods . We investigated the association between  p73  DNP 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 between  p73  DNP and PCa risk, a significant inverse relationship between  p73  DNP and PCa aggressiveness (AT/AT + GC/AT versus GC/GC, OR = 0.55, 95%Cl = 0.31–0.99) was detected. Also,  p73  DNP 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 the  p73  DNP have lower levels of ∆Np73 relative to TAp73 ( P  < 0.001).  Conclusions . Our findings are consistent with an association between  p73  DNP and low risk for PCa aggressiveness by increasing the expressed TAp73/∆Np73 protein isoform ratio.

Role ofp73Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance