title: Role of the functional variant (-652T>G) in the XRCC4 promoter in prostate cancer.
abstract: Several genes encoding DNA repair molecules have been proposed as cancer-susceptibility genes. Many studies have suggested that SNPs in XRCC4 could be implicated in altering the risk of prostate cancer (PCa). We examined the role of the functional variant (-652T>G) in the XRCC4 promoter in PCa. The transcriptional activity of XRCC4 gene was measured by luciferase assay. We performed real-time PCR/immunohistochemical assay to verify the association between expression level of XRCC4 mRNA/protein and XRCC4 -652T>G polymorphism. In addition, electrophoretic mobility shift assay (EMSA) was used to confirm whether this polymorphism has an effect on binding ability of the transcription factor. We found that the G variant significantly increased the transcription activity of the XRCC4 gene and the binding ability of transcriptional factor GATA-1 to the XRCC4 promoter. Furthermore, the results suggested that the XRCC4 protein and mRNA were overexpressed in individuals who carried the -652G allele compared to carriers of the -652T allele. In addition, the expression of XRCC4 in PCa tissues was lower than in adjacent normal tissues. Our data suggest that the XRCC4 promoter -652G>T polymorphism is functional and may influence genetic susceptibility to prostate cancer. Case-control studies are required to validate our findings in the future.
authors.affiliation: Department of Urology, Second People's Hospital of Wuxi Affiliated to Nanjing Medical University, 68 Zhongshan Road, Wuxi, 214002, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Shao
authors.forename: JiuMing
authors.initials: J
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: XiaoJie
authors.initials: X
authors.lastname: Lu
authors.forename: NingHan
authors.initials: N
authors.lastname: Feng
mesh_terms: D045744:Cell Line, Tumor; D002681:China; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases; D008297:Male; D010957:Plasmids / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C101467:XRCC4 protein, human; D008156:Luciferases
references.citation: J Natl Cancer Inst. 2000 Sep 20;92(18):1537
references.pmid: 10995816
references.citation: Mol Med Rep. 2008 Jul-Aug;1(4):525-30
references.pmid: 21479444
references.citation: DNA Repair (Amst). 2007 Jul 1;6(7):923-35
references.pmid: 17363343
references.citation: Oncol Rep. 2010 Oct;24(4):1079-85
references.pmid: 20811692
references.citation: Cancer. 2012 Jan 15;118(2):528-35
references.pmid: 21717429
references.citation: DNA Repair (Amst). 2004 Jan 5;3(1):43-50
references.pmid: 14697758
references.citation: CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
references.pmid: 22237781
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18597-602
references.pmid: 17124166
references.citation: Eur J Cancer Prev. 2010 Jul;19(4):299-307
references.pmid: 20389250
references.citation: Anticancer Res. 2010 Jul;30(7):2727-30
references.pmid: 20683005
references.citation: DNA Cell Biol. 2010 Nov;29(11):669-74
references.pmid: 20590474
references.citation: J Urol. 1974 Jan;111(1):58-64
references.pmid: 4813554
references.citation: Mol Biol Rep. 2012 Feb;39(2):1667-75
references.pmid: 21617942
references.citation: Cancer Sci. 2010 May;101(5):1247-54
references.pmid: 20331623
references.citation: Genetics. 1988 Nov;120(3):849-52
references.pmid: 3224810
references.citation: Pathologe. 1987 May;8(3):138-40
references.pmid: 3303008