Polymorphisms in DNA Repair Genes and Risk of Glioma and Meningioma

Ke-Qin Luo,Shi-Qing Mu,Ji-Cai Peng,Zhong-Xue Wu,Yi-Ni Shi

doi:10.7314/apjcp.2013.14.1.449

Abstract

Polymorphisms in DNA repair genes have been shown to influence DNA repair processes and to modify cancer susceptibility. Here we conducted a case-control study to assess the role of potential SNPs of DNA repair genes on the risk of glioma and meningioma. We included 297 cases and 458 cancer-free controls. Genotyping of XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met, XRCC4 Ala247Ser, ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were performed in a 384-well plate format on the Sequenom MassARRAY platform. XRCC1 Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793 did not follow the HWE in control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2 Arg188His rs3218536 and ERCC2 Asp312Asn rs1799793 were significantly different between cases and controls (P<0.05). We found XRCC1 399G/G, XRCC1 194 T/T and XRCC3 241T/T were associated with a higher risk when compared with the wild-type genotype. For ERCC5 Asp1558His, we found G/G genotype was associated with elevated susceptibility. In conclusion, our study has shown that XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of gliomas and meningiomas. This finding could be useful in identifying the susceptibility genes for these cancers.

Highlights

Gliomas and meningiomas are common central nervous system tumors, and account for about 80% of all the central nervous system tumors (Parkin et al, 2005)
Our study has shown that XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of gliomas and meningiomas
This study has examined the risk of glioma and meningioma in 1127 polymorphisms of DNA repair genes, and has indicated BR1P1 rs4968541 is associated with the risk of meningioma (OR=1.6, 95%confidence intervals (CIs)=1.3-1.9) and CHAF1A rs243356 is related to a moderate higher risk of glioma (OR=1.3, 95%CI=1.1-1.5)

Summary

Introduction

Gliomas and meningiomas are common central nervous system tumors, and account for about 80% of all the central nervous system tumors (Parkin et al, 2005). The morbidity of glioma is relatively low compared with other cancers, it is the most serious cancer in humans and influences the function of all the organs, and its prognosis is poor relative to other tumors (Bondy et al, 2008). The only confirmed environmental risk factors are ionizing radiation and ultraviolet rays, and the low exposure of them would protect the occurrence of this cancer (Sadetzki et al, 2007; Davis et al, 2008). The ionizing radiation and ultraviolet rays induce DNA damage, such as oxidative DNA damage, single- and double-strand breaks in DNA chains, and DNA-protein cross-links (Vogelstein and Kinzler, 2004). These damages would cause the development of cancer. Three main complex systems of DNA repairs pathways prevent the DNA damage and prevent mutagenesis, including baseexcision repair (BER), nucleotide excision repair (NER), and homologous recombination repair (HRR) (National Academies of Science, 2006)

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