A novel variable number of tandem repeats (VNTR) polymorphism containing Sp1 binding elements in the promoter of XRCC5 is a risk factor for human bladder cancer.
X-ray repair cross-complementing 5 (XRCC5) is a gene involved in repair of DNA double-strand breaks. Abnormal expression of the XRCC5 protein is associated with genomic instability and an increased incidence of cancers. In our study, a polymorphism with a variable number of tandem repeats (21-bp repeat elements at position -201 to -160 relative to the initiation of transcription) in the promoter of XRCC5 was identified. As determined with gel-shift and super-shift assays, the binding affinity of the transcription factor Sp1 to the allele with two 21-bp repeats was greater than that for the allele with one 21-bp repeat. As established with a reporter assay, plasmids containing zero or one repeat element had higher transcriptional activities than plasmids containing two repeat elements. Furthermore, fewer tandem repeats in the promoter of XRCC5 was associated with enhanced levels of the XRCC5 protein in bladder cancer patients. Although, in a case-control study, the different genotypes were not associated with the risk of bladder cancer, individuals not carrying the two tandem repeats allele had an increased risk of bladder cancer compared with those carrying the allele with two repeats. These results indicated that, at least in a population in southeastern China, this polymorphism in the promoter of XRCC5 could regulate the expression of XRCC5 and thereby contribute to susceptibility to bladder cancer.
Wang
Shouyu
S
Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Wang
Meilin
M
Yin
Shiwei
S
Fu
Guangbo
G
Li
Chunping
C
Chen
Rui
R
Li
Aiping
A
Zhou
Jianwei
J
Zhang
Zhengdong
Z
Liu
Qizhan
Q
D000368:Aged; D001483:Base Sequence; D004265:DNA Helicases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D016329:Sp1 Transcription Factor / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
D009687:Nuclear Proteins; D016329:Sp1 Transcription Factor; D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen