Journal Article

Gamma-radiation sensitivity and polymorphisms in <i>RAD51L1</i> modulate glioma risk

Yanhong Liu, Sanjay Shete, Li-E Wang, Randa El-Zein, Carol J. Etzel, Fu-Wen Liang, Georgina Armstrong, Spyros Tsavachidis, Mark R. Gilbert, Kenneth D. Aldape, Jinliang Xing, Xifeng Wu, Qingyi Wei and Melissa L. Bondy

in Carcinogenesis

Volume 31, issue 10, pages 1762-1769
Published in print October 2010 | ISSN: 0143-3334
Published online July 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq141
Gamma-radiation sensitivity and polymorphisms in RAD51L1 modulate glioma risk

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  • Clinical Cytogenetics and Molecular Genetics

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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.

Journal Article.  5144 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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