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"Gamma-Radiation Sensitivity and Polymorphisms in RAD51L1 Modulate Glioma Risk." |
Liu Y, Shete S, Wang LE, El-Zein R, Etzel CJ, Liang FW, Armstrong G, Tsavachidis S, Gilbert M, Aldape K, Xing J, Wu X, Wei Q, Bondy ML |
Published July 7, 2010 in Carcinogenesis .
Pubmed ID: 20610542
Abstract:
| 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 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 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. |
This publication refers to following REPAIRtoire entries:
| Genes |
Last modification of this entry: Oct. 6, 2010
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