Limits...
Role of p73 Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance.

Carastro LM, Lin HY, Park HY, Kim D, Radlein S, Hampton KK, Hakam A, Zachariah B, Pow-Sang J, Park JY - Prostate Cancer (2014)

Bottom Line: Methods.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).Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Biochemistry & Physics, University of Tampa, Tampa, FL 33606, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Association between rs1801173 and overall survival (a) and prostate cancer specific survival (b). A role of p73 DNP in prostate cancer progression and aggressiveness was investigated. p73 DNP is marginally associated with overall death (dominant model, hazard ratio (HR) = 0.76, 95%CI = 0.57–1.00, P = 0.053 by Cox regression adjusted for age) as well as PCa specific death (HR = 0.69, 95%CI = 0.45–1.06, P = 0.09 by the competing risk regression adjusted for age).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4109114&req=5

fig1: Association between rs1801173 and overall survival (a) and prostate cancer specific survival (b). A role of p73 DNP in prostate cancer progression and aggressiveness was investigated. p73 DNP is marginally associated with overall death (dominant model, hazard ratio (HR) = 0.76, 95%CI = 0.57–1.00, P = 0.053 by Cox regression adjusted for age) as well as PCa specific death (HR = 0.69, 95%CI = 0.45–1.06, P = 0.09 by the competing risk regression adjusted for age).

Mentions: We investigate a role of p73 DNP in prostate cancer progression and aggressiveness. The p73 DNP was significantly associated with high Gleason score [37, 40, 41] (dominant model, odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31–0.99) among Caucasians (Table 2). The similar association was not observed in African American patients. Interestingly, p73 DNP is marginally associated with overall death (dominant model, hazard ratio (HR) = 0.76, 95%CI = 0.57–1.00, P = 0.053) as well as PCa specific death (HR = 0.69, 95%CI = 0.45–1.06, P = 0.09, Table 2 and Figure 1). The survival analyses were not performed for African American patients due to a small sample size.


Role of p73 Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance.

Carastro LM, Lin HY, Park HY, Kim D, Radlein S, Hampton KK, Hakam A, Zachariah B, Pow-Sang J, Park JY - Prostate Cancer (2014)

Association between rs1801173 and overall survival (a) and prostate cancer specific survival (b). A role of p73 DNP in prostate cancer progression and aggressiveness was investigated. p73 DNP is marginally associated with overall death (dominant model, hazard ratio (HR) = 0.76, 95%CI = 0.57–1.00, P = 0.053 by Cox regression adjusted for age) as well as PCa specific death (HR = 0.69, 95%CI = 0.45–1.06, P = 0.09 by the competing risk regression adjusted for age).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4109114&req=5

fig1: Association between rs1801173 and overall survival (a) and prostate cancer specific survival (b). A role of p73 DNP in prostate cancer progression and aggressiveness was investigated. p73 DNP is marginally associated with overall death (dominant model, hazard ratio (HR) = 0.76, 95%CI = 0.57–1.00, P = 0.053 by Cox regression adjusted for age) as well as PCa specific death (HR = 0.69, 95%CI = 0.45–1.06, P = 0.09 by the competing risk regression adjusted for age).
Mentions: We investigate a role of p73 DNP in prostate cancer progression and aggressiveness. The p73 DNP was significantly associated with high Gleason score [37, 40, 41] (dominant model, odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.31–0.99) among Caucasians (Table 2). The similar association was not observed in African American patients. Interestingly, p73 DNP is marginally associated with overall death (dominant model, hazard ratio (HR) = 0.76, 95%CI = 0.57–1.00, P = 0.053) as well as PCa specific death (HR = 0.69, 95%CI = 0.45–1.06, P = 0.09, Table 2 and Figure 1). The survival analyses were not performed for African American patients due to a small sample size.

Bottom Line: Methods.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).Conclusions.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Biochemistry & Physics, University of Tampa, Tampa, FL 33606, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus