A Comprehensive Meta-analysis of Genetic Associations Between Key Polymorphic Loci in DNA Repair Genes and Glioma Risk

Abstract

Genetic variants found in DNA repair genes (ERCC1, rs3212986; ERCC2, rs13181; ERCC4, rs1800067; ERCC5, rs17655; XRCC1, rs1799782, rs25487, rs25489; XRCC3, rs861539) have been reported to have an ambivalent association with the development of glioma. In the present study, a meta-analysis was conducted to confirm the relationship, taking heterogeneity of population into consideration. We analyzed 21 articles of 6 genes along with 8 single nucleotide polymorphisms (SNPs) (24,078 cases and 30,926 healthy individuals), which assessed the relationship between nucleotide excision, base excision, double-strand break repair gene, and the development of glioma under five models. All statistical analysis was implemented by the software of R 3.2.1, and the relationships between key polymorphic loci in DNA repair genes and glioma were quantified by the pooled odds ratio (OR) and 95 % confidential intervals. Overall, the synthesized evidence demonstrated that the SNP of rs13181 and rs1799782 significantly increased the risk of glioma whereas SNP of rs1800067 were significantly associated with a decrease in the risk of glioma. Additionally, subgroup analyses of 8 SNPs by ethnicity indicated that the mutation of rs13181, rs1800067 were apparently protective factors of glioma among Asians, while the mutation of rs13181 was a risk factors of glioma in Caucasians. Furthermore, the mutation of rs1799782 significantly raises the risk of glioma for Asian. Our study suggested that rs13181*C and rs1799782*A are risk alleles for glioma; rs1800067*A are beneficial alleles for decreased susceptibility to glioma. Future studies with large sample size and other races are strongly recommended to confirm the results from this study.

Keywords: DNA repair genes; ERCC; Genetic polymorphisms; Glioma; Meta-analysis; XRCC.