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.
This meta-analysis suggests that glioma susceptibility is associated with rs1799782 and rs25487 of X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1), rs1805377 of XRCC4, rs1800067 of excision repair cross-complementing rodent repair deficiency complementation group 4 (ERCC4) and rs3212986 of ERCC1 in Asian population, and rs12917 of O-6-methylguanine-DNA methyltransferase (MGMT) and rs1136410 of poly(ADP-ribose) polymerase 1 (PARP1) in Caucasian population.
Current evidence indicated that XRCC1Arg194Trp polymorphism was associated with increased risk for glioma, especially in Asians; however, relevant studies involving other ethnic groups are required to validate our findings in further.
Nevertheless, large-scale, well-designed and population-based studies are needed to further evaluate gene-gene and gene-environment interactions, as well as to measure the combined effects of these XRCC1 variants on glioma risk.
When stratified by the grade of glioma, patients with WHO IV glioma had a significantly higher frequency of XRCC1 194 TT (OR = 1.60, 95 % CI = 1.02, 2.51; P = 0.04) and XRCC1 399 AA genotype (OR = 1.59, 95 % CI = 1.04, 2.42; P = 0.03).
These preliminary findings indicate that the c.1471G>A genetic polymorphism of XRCC1 has the potential to influence glioma susceptibility, and might be used as molecular marker for assessing glioma risk.
A total of 11 studies (3,810 cases and 6,079 controls), 7 studies (2,928 cases and 5,048 controls), and 4 studies (1,461 cases and 2,593 controls) were finally included in the analyses of the association between XRCC1Arg399Gln, Arg194Trp, and Arg280His polymorphisms and glioma risk, respectively.