There are four main pathways involved in repairing DNA damage, nucleotide excision repair (NER), base excision repair (BER), double-strand break repair (DSBR), and mismatch repair (MMR). XRCC1 and ERCC2 encode proteins that are involved in the BER and NER pathways, respectively, and polymorphisms in these genes may change a cell’s DNA repair efficiency. This in turn may be related to the development of several types of cancers, including lung, colorectal, breast, ovary, and thyroid cancers, esophageal carcinoma, and even brain tumors [9–11].
The XRCC group is an important component of the BER system, which is the predominant DNA repair pathway for small errors resulting from oxidation and alkylation damage. The proper functioning of the BER system may prevent the activation of oncogenes or the inactivation of tumor suppression genes and thereby reduce the risk of cancer development. The XRCC1 gene is located on chromosome 19q13.2-13.2, is 33 kb in size, and consists of 17 exons. The XRCC1 protein coordinates several protein-protein interactions, including those between DNA ligase III, DNA polymerase, and poly ADP-ribose polymerase, which together play an important role in DNA repair. Numerous studies shown a positive correlation between SNPs of XRCC1 and the risk of developing glial neoplasms, and the most common being Arg194Trp (rs1799782), Arg399Gln (rs25487), and Arg280His (rs25489) [7, 9, 12, 13].
Our current systematic review included eleven published articles on XRCC1 rs1799782, which contained contradictory findings. For instance, studies by Gao et al. , Li et al. , Zhou et al.  and Wang et al.  reported no association between the XRCC1 rs1799782 SNP and the risk of developing gliomas. However, other studies reported an increased risk, including those by Hu et al.  and Rajaraman et al. . Mean while, Liu et al. , Xu et al.  and Pan et al.  reported an increased risk for glioma specific for the TT genotypes in an Asian population. Custodio et al.  reported an increased risk for gliomas in Caucasians with the XRCC1 rs1799782 SNP (Brazilian population), but they also observed improved survival in the presence of the 194Trp allele. Finally, in the study published by Fan et al.  there was an increased risk for gliomas in participants that had TT or CT + TT genotypes (Table 2) [14–24].
Due to the discrepancies in the published results, we performed this meta-analysis and found for healthy individuals an increased risk for the development of glial tumors only in Asians with the TT genotype of the XRCC1 rs1799782 as an association was not observed with the CT and/or CT + TT genotypes. These results were similar to the meta-analyses by Li et al. , He et al. , and Zhang et al. . However, in none of those studies was the data analysis broken down by observed population type [25–27]. Contrary to our study, a review by Sun et al. , reported an increased risk associated with the TT genotype in the general population, but no association when individually analyzed in the Asian and Caucasian populations .
Lu et al.  reviewed sixteen published papers and reported increased risk only for Asians with TT and TT + CT genotype in their meta-analysis. Xu et al.  found an increased risk only in Asians with CT + TT genotype and in both Asians and Caucasians with TT genotype. There are currently also systematic reviews in the literature that include meta-analysis and report a relationship between the XRCC1 rs1799782 polymorphism and its genotypes with the development of glial tumors [31–33].
The ERCC2 gene is located on chromosome 19q13.3 and encodes a protein responsible for DNA repair as part of the NER pathway. There are published reports on the relationship between some ERCC2 SNPs and the risk of systemic tumors with the most studied being ERCC2 Lys751Gln (rs13181). This polymorphism is characterized by the replacement of thymine (T) by guanine (G) at the locus 751, which changes the enzymatic activity of some encoded proteins, such as helicase, and can be associated with several types of cancers, including gastric, esophageal, hepatocellular carcinoma, non-small cell lung, prostate, skin, and bladder cancers, as well as gliomas . Our current study reviewed and analyzed ten published reports that included five based on Asian populations, four based on Caucasian populations, and one that included both populations and the genotypes studied in these reports were AC, CC, GG, and TG.
Similar to the results regarding the XRCC1 polymorphisms, the findings for ERCC2 rs13181 polymorphisms are highly contradictory. Six reports demonstrate no relationship between ERCC2 rs13181 polymorphisms and the risk of developing glial tumors. However, the studies by Gao et al.  and Chen et al.  reported increased risks of gliomas while the reports by McKean-Cowdin  and Rodriguez-Hernandez et al.  showed a decrease risk in the presence of the AGC haplotype and C allele, respectively.
Based on meta-analysis, the AC genotypes of ERCC2 rs13181 in Asians and Caucasians and the CC genotypes in Caucasians were associated to an increased risk of gliomas. This result corroborates the findings reported by Qian et al. , who reviewed fifteen studies and conducted a meta-analysis . These investigators reported increased risks for the development of glial cell tumors only in Asians with the CC and AC genotypes (Figs. 2 and 3).
In our current review and analysis, the GG and TG genotypes showed no relationship with the development of glial tumors, corroborating the studies by Xin et al.  and Zhou et al.  (Fig. 2 and Fig. 3). However, contrary results were described in the reviews and meta-analyses by Cui et al.  and Jia et al. , who found increased risks only in Asian populations and with the TG genotype. On the other hand, Huang et al.  found increased risks in the general population for patients with either TG or GG genotypes.
Although the meta-analysis shows the importance of SNPs XRCC1 rs1799782 TT, ERCC2 rs13181 AC and CC in the development of gliomas in certain populations, the high heterogeneity between studies and the presence of publication biases evidenced in some Plot Funnel, show the need for further multicenter studies with larger samples, more uniform methodologies and research with different ethnic groups in order to establish the association of these polymorphisms with the risk of developing gliomas.
The studies presented in our current review and analysis had limitations, which thereby contributed to limitations of our study. These included the fact that most all of them used only one population type, which prevents the extrapolation of the results to other ethnic groups. Furthermore, in most of the studies, the samples were collected from only a single hospital, increasing the potential for selection bias. Finally, in most of the studies the interactions between genes, environmental factors, and even the loci of the polymorphisms were not considered, which are factors that may influence the risk of developing gliomas.