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Open Access Highly Accessed Research article

Genetic polymorphisms of DNA double-strand break repair pathway genes and glioma susceptibility

Peng Zhao1*, Peng Zou1, Lin Zhao1, Wei Yan2, Chunsheng Kang3, Tao Jiang2 and Yongping You1*

Author Affiliations

1 Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

2 Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, 100050, China

3 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300052, China

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BMC Cancer 2013, 13:234  doi:10.1186/1471-2407-13-234

Published: 10 May 2013

Abstract

Background

Genetic variations in DNA double-strand break repair genes can influence the ability of a cell to repair damaged DNA and alter an individual’s susceptibility to cancer. We studied whether polymorphisms in DNA double-strand break repair genes are associated with an increased risk of glioma development.

Methods

We genotyped 10 potentially functional single nucleotide polymorphisms (SNPs) in 7 DNA double-strand break repair pathway genes (XRCC3, BRCA2, RAG1, XRCC5, LIG4, XRCC4 and ATM) in a case–control study including 384 glioma patients and 384 cancer-free controls in a Chinese Han population. Genotypes were determined using the OpenArray platform.

Results

In the single-locus analysis there was a significant association between gliomas and the LIG4 rs1805388 (Ex2 +54C>T, Thr9Ile) TT genotype (adjusted OR, 3.27; 95% CI, 1.87-5.71), as well as the TC genotype (adjusted OR, 1.62; 95% CI, 1.20-2.18). We also found that the homozygous variant genotype (GG) of XRCC4 rs1805377 (IVS7-1A>G, splice-site) was associated with a significantly increased risk of gliomas (OR, 1.77; 95% CI, 1.12-2.80). Interestingly, we detected a significant additive and multiplicative interaction effect between the LIG4 rs1805388 and XRCC4 rs1805377 polymorphisms with an increasing risk of gliomas. When we stratified our analysis by smoking status, LIG4 rs1805388 was associated with an increased glioma risk among smokers.

Conclusions

These results indicate for the first time that LIG4 rs1805388 and XRCC4 rs1805377, alone or in combination, are associated with a risk of gliomas.

Keywords:
DNA double-strand breaks (DSBs); Single nucleotide polymorphisms (SNPs); Glioma; Susceptibility