Tagging SNPs in non-homologous end-joining pathway genes and risk of glioma.

Journal Article (Journal Article)

Ionizing radiation is known to cause DNA damage, including single-strand and double-strand DNA breaks (DSBs), and the unrepair of DNA damage, particularly DSBs, may cause chromosome aberrations. Although the etiology of gliomas remains unclear, exposure to ionizing radiation has been identified as the only established risk factor. We hypothesized that polymorphisms of candidate genes involved in the DSBs repair pathway may contribute to susceptibility to glioma. We used a haplotype-based approach to investigate the role of 22 tagging single-nucleotide polymorphisms (tSNPs) of XRCC5, XRCC6 and XRCC7 in 771 glioma patients and 752 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the unconditional logistic regression, haplotypes were inferred by the HAPLO.STAT program and gene-gene interactions were evaluated by the multifactor dimensionality reduction method. We found that, in the single-locus analysis, glioma risk was statistically significantly associated with three XRCC5 tSNPs (SNP1 rs828704, SNP6 rs3770502 and SNP7 rs9288516, P = 0.005, 0.042 and 0.003, respectively), one XRCC6 tSNP (SNP4 rs6519265, P = 0.044) but none of XPCC7 tSNPs. Haplotype-based association analysis revealed that gliomas risk was statistically significantly associated with one protective XRCC5 haplotype "CAGTT," accounting for a 40% reduction (OR = 0.60, 95% CI = 0.43-0.85) in glioma risk, and some positive gene-gene interactions were also evident. In conclusion, genetic variants of the genes involved in the DSB repair pathway may play a role in the etiology of glioma.

Full Text

Duke Authors

Cited Authors

  • Liu, Y; Zhang, H; Zhou, K; Chen, L; Xu, Z; Zhong, Y; Liu, H; Li, R; Shugart, YY; Wei, Q; Jin, L; Huang, F; Lu, D; Zhou, L

Published Date

  • September 2007

Published In

Volume / Issue

  • 28 / 9

Start / End Page

  • 1906 - 1913

PubMed ID

  • 17389609

International Standard Serial Number (ISSN)

  • 0143-3334

Digital Object Identifier (DOI)

  • 10.1093/carcin/bgm073


  • eng

Conference Location

  • England