Source:http://linkedlifedata.com/resource/pubmed/id/16652158
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
25
|
| pubmed:dateCreated |
2006-6-15
|
| pubmed:abstractText |
X-ray repair cross-complementing 1 (XRCC1) plays a key role in DNA base excision repair and cells lacking its activity are hypersensitive to DNA damage. Recently, we reported a SNP (rs3213245, -77T>C) in the XRCC1 gene 5' untranslated region (UTR) was significantly associated with the risk of developing esophageal squamous-cell carcinoma. Computer analysis predicted that this SNP was in the core of Sp1-binding motif, which suggested its functional significance. Gel shift and super shift assays confirmed that -77T>C polymorphic site in the XRCC1 promoter was within the Sp1-binding motif and the T>C substitution greatly enhanced the binding affinity of Sp1 to this region. Luciferase assays indicated that the Sp1-high-affinity C-allelic XRCC1 promoter was associated with a reduced transcriptional activity. The association between -77T>C and three other amino-acid substitution-causing polymorphisms in XRCC1 and risk of lung cancer was examined in 1024 patients and 1118 controls and the results showed that only the -77T>C polymorphism was significantly associated with an increased risk of developing lung cancer. Multivariate logistic regression analysis found that an increased risk of lung cancer was associated with the variant XRCC1 -77 genotypes (TC and CC) compared with the TT genotype (OR=1.46, 95% CI=1.18-1.82; P=0.001) and the increased risk was more pronounced in smokers (OR=1.63, 95% CI=1.20-2.21) than in non-smokers (OR=1.28, 95% CI=0.94-1.76). Taken together, these results showed that the functional SNP -77T>C in XRCC1 5'UTR was associated with cancer development owing to the decreased transcriptional activity of C-allele-containing promoter with higher affinity to Sp1 binding.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0950-9232
|
| pubmed:author |
pubmed-author:ChewAA,
pubmed-author:FOXJ JJJ,
pubmed-author:HaoBB,
pubmed-author:LUMM,
pubmed-author:LiangGG,
pubmed-author:LinDD,
pubmed-author:MibeMM,
pubmed-author:SunTT,
pubmed-author:TaoTT,
pubmed-author:WangHH,
pubmed-author:WeiQQ,
pubmed-author:ZhaiSS,
pubmed-author:ZhangLL,
pubmed-author:ZhangXX,
pubmed-author:ZhouYY
|
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
25
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3613-20
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:16652158-Adult,
pubmed-meshheading:16652158-Aged,
pubmed-meshheading:16652158-Base Sequence,
pubmed-meshheading:16652158-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:16652158-Case-Control Studies,
pubmed-meshheading:16652158-Cell Line, Tumor,
pubmed-meshheading:16652158-Computer Simulation,
pubmed-meshheading:16652158-DNA-Binding Proteins,
pubmed-meshheading:16652158-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:16652158-Female,
pubmed-meshheading:16652158-Genotype,
pubmed-meshheading:16652158-Humans,
pubmed-meshheading:16652158-Lung Neoplasms,
pubmed-meshheading:16652158-Male,
pubmed-meshheading:16652158-Middle Aged,
pubmed-meshheading:16652158-Polymorphism, Genetic,
pubmed-meshheading:16652158-Promoter Regions, Genetic,
pubmed-meshheading:16652158-Risk Factors
|
| pubmed:year |
2006
|
| pubmed:articleTitle |
A novel T-77C polymorphism in DNA repair gene XRCC1 contributes to diminished promoter activity and increased risk of non-small cell lung cancer.
|
| pubmed:affiliation |
Department of Biology Sciences and Biotechnology, Tsinghua University, Beijing, China.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|