title: Role of p73 Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance.
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.
authors.affiliation: Department of Chemistry, Biochemistry & Physics, University of Tampa, Tampa, FL 33606, USA.
authors.forename: L Michael
authors.initials: LM
authors.lastname: Carastro
authors.affiliation: Department of Biostatistics, Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: Hyun Y
authors.initials: HY
authors.lastname: Park
authors.affiliation: Department of Molecular Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Donghwa
authors.identifier: 0000-0003-2233-7168
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: Selina
authors.identifier: 0000-0001-8281-5999
authors.initials: S
authors.lastname: Radlein
authors.affiliation: Department of Chemistry, Biochemistry & Physics, University of Tampa, Tampa, FL 33606, USA.
authors.forename: Kaia K
authors.initials: KK
authors.lastname: Hampton
authors.affiliation: Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Ardeshir
authors.initials: A
authors.lastname: Hakam
authors.affiliation: Genitourinary Program, James Haley VA Hospital, Tampa, FL 33612, USA.
authors.forename: Babu
authors.initials: B
authors.lastname: Zachariah
authors.affiliation: Genitourinary Program, Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Julio
authors.initials: J
authors.lastname: Pow-Sang
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: Jong Y
authors.initials: JY
authors.lastname: Park
references.citation: Mol Biol Rep. 2012 Feb;39(2):1731-8
references.pmid: 21617940
references.citation: Int J Biochem Cell Biol. 2011 Apr;43(4):482-6
references.pmid: 21216303
references.citation: Biochem Genet. 2006 Dec;44(11-12):543-50
references.pmid: 17136456
references.citation: Mol Carcinog. 2009 Sep;48(9):790-800
references.pmid: 19204927
references.citation: Int J Gynecol Cancer. 2009 May;19(4):572-7
references.pmid: 19509552
references.citation: Carcinogenesis. 2004 Oct;25(10):1911-6
references.pmid: 15180941
references.citation: Appl Immunohistochem Mol Morphol. 2010 Dec;18(6):546-54
references.pmid: 20733477
references.citation: Gene. 2011 Sep 15;484(1-2):42-6
references.pmid: 21672615
references.citation: Med Oncol. 2012 Dec;29(5):3216-21
references.pmid: 22535334
references.citation: Virchows Arch. 2010 Sep;457(3):359-68
references.pmid: 20644956
references.citation: Breast Cancer. 2003;10(4):307-11
references.pmid: 14634508
references.citation: Med Oncol. 2013 Jun;30(2):515
references.pmid: 23443851
references.citation: World J Urol. 2014 Apr;32(2):399-405
references.pmid: 23765315
references.citation: Asian Pac J Cancer Prev. 2003 Apr-Jun;4(2):107-12
references.pmid: 12875622
references.citation: Urology. 2013 Jun;81(6):1202-8
references.pmid: 23561706
references.citation: Mutagenesis. 2011 Jul;26(4):573-81
references.pmid: 21502193
references.citation: World J Gastroenterol. 2010 Sep 21;16(35):4448-54
references.pmid: 20845513
references.citation: Tumour Biol. 2013 Feb;34(1):293-9
references.pmid: 23065572
references.citation: DNA Cell Biol. 2012 Feb;31(2):224-9
references.pmid: 21711160
references.citation: Oncol Rep. 2004 Nov;12(5):1131-7
references.pmid: 15492805
references.citation: Dis Esophagus. 2007;20(4):290-6
references.pmid: 17617876
references.citation: Mol Carcinog. 2007 Feb;46(2):100-5
references.pmid: 17013834
references.citation: Cancer Epidemiol Biomarkers Prev. 2006 Jan;15(1):158-61
references.pmid: 16434604
references.citation: Mol Carcinog. 2013 May;52(5):387-91
references.pmid: 22228141
references.citation: Indian J Hum Genet. 2013 Jul;19(3):293-300
references.pmid: 24339541
references.citation: Br J Cancer. 2001 Nov 16;85(10):1499-503
references.pmid: 11720435
references.citation: Oncogene. 2000 Nov 9;19(47):5413-8
references.pmid: 11103943
references.citation: Eur J Cancer. 2007 Jun;43(9):1361-72
references.pmid: 17428654
references.citation: DNA Cell Biol. 2012 Feb;31(2):230-7
references.pmid: 22011187
references.citation: J Exp Med. 2002 Sep 16;196(6):765-80
references.pmid: 12235210
references.citation: Cancer Res. 2004 Oct 1;64(19):6863-6
references.pmid: 15466174
references.citation: Carcinogenesis. 2008 Nov;29(11):2120-5
references.pmid: 18701437
references.citation: Cancer Lett. 2004 Mar 8;205(1):55-60
references.pmid: 15036661
references.citation: Carcinogenesis. 2005 Jan;26(1):103-7
references.pmid: 15485994
references.citation: PLoS One. 2012;7(4):e35522
references.pmid: 22523600
references.citation: Cancer Lett. 2002 Jul 8;181(1):81-5
references.pmid: 12430182
references.citation: Cell Death Differ. 2006 Jun;13(6):962-72
references.pmid: 16601753
references.citation: J Invest Dermatol. 2008 Jun;128(6):1585-8
references.pmid: 18049450
references.citation: Mutat Res. 2009 Apr 30;675(1-2):60-5
references.pmid: 19386249
references.citation: J Clin Pathol. 2005 Nov;58(11):1175-9
references.pmid: 16254107
references.citation: Urology. 2013 Jul;82(1):53-8
references.pmid: 23806388
references.citation: Cancer Lett. 2005 Mar 10;219(2):183-90
references.pmid: 15723718
references.citation: Arch Med Res. 2011 Feb;42(2):122-7
references.pmid: 21565625
references.citation: Int J Cancer. 2005 Apr 10;114(3):455-60
references.pmid: 15578704
references.citation: Leuk Lymphoma. 2004 May;45(5):957-64
references.pmid: 15291355
references.citation: BMC Cancer. 2009 May 08;9:137
references.pmid: 19426493
references.citation: Cancer. 2006 Aug 1;107(3):521-9
references.pmid: 16773619