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http://purl.uniprot.org/citations/20610542http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20610542http://www.w3.org/2000/01/rdf-schema#comment"

Background

DNA strand breaks pose the greatest threat to genomic stability. Genetically determined mutagen sensitivity predisposes individuals to a variety of cancers, including glioma. However, polymorphisms in DNA strand break repair genes that may determine mutagen sensitivity are not well studied in cancer risk, especially in gliomas.

Methods

We correlated genotype data for tag single-nucleotide polymorphisms (tSNPs) of DNA strand break repair genes with a gamma-radiation-induced mutagen sensitivity phenotype [expressed as mean breaks per cell (B/C)] in samples from 426 glioma patients. We also conducted analysis to assess joint and haplotype effects of single-nucleotide polymorphisms (SNPs) on mutagen sensitivity. We further validate our results in an independent external control group totaling 662 subjects.

Results

Of the 392 tSNPs examined, we found that mutagen sensitivity was modified by one tSNP in the EME2 gene and six tSNPs in the RAD51L1 gene (P < 0.01). Among the six RAD51L1 SNPs tested in the validation set, one (RAD51L1 rs2180611) was significantly associated with mutagen sensitivity (P = 0.025). Moreover, we found a significant dose-response relationship between the mutagen sensitivity and the number of adverse tSNP genotypes. Furthermore, haplotype analysis revealed that RAD51L1 haplotypes F-A (zero adverse allele) and F-E (six adverse alleles) exhibited the lowest (0.42) and highest (0.93) mean B/C values, respectively. A similar dose-response relationship also existed between the mutagen sensitivity and the number of adverse haplotypes.

Conclusion

These results suggest that polymorphisms in and haplotypes of the RAD51L1 gene, which is involved in the double-strand break repair pathway, modulate gamma-radiation-induced mutagen sensitivity."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.org/dc/terms/identifier"doi:10.1093/carcin/bgq141"xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Liu Y."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Wu X."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Wei Q."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Shete S."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Xing J."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Armstrong G."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Wang L.E."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Aldape K.D."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Gilbert M.R."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Bondy M.L."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Tsavachidis S."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"El-Zein R."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Etzel C.J."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/author"Liang F.W."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/name"Carcinogenesis"xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/pages"1762-1769"xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/title"Gamma-radiation sensitivity and polymorphisms in RAD51L1 modulate glioma risk."xsd:string
http://purl.uniprot.org/citations/20610542http://purl.uniprot.org/core/volume"31"xsd:string
http://purl.uniprot.org/citations/20610542http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20610542
http://purl.uniprot.org/citations/20610542http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20610542
http://purl.uniprot.org/uniprot/#_A0A0C4DGV9-mappedCitation-20610542http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20610542
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