We genotyped constitutive variants ERCC1C8092A and ERCC2 K751Q and R156R in approximately 450 adults with glioma and 500 controls from two independent population-based series, uniformly reviewed patients' tumors to determine histopathologic category, and determined a variety of tumor markers among astrocytic tumors.
In the single-locus analysis, six single-nucleotide polymorphisms [ERCC1 3' untranslated region (UTR), XRCC1 R399Q, APEX1 E148D, PARP1 A762V, MGMT F84L, and LIG1 5'UTR] showed a significant association with glioma risk.
We determined the presence of the A versus C polymorphism at nucleotide 8092 of ERCC1 using a single-strand conformational polymorphism assay and DNA sequencing in adults with glioma and controls from a population-based study.
In conclusion, our study suggests that ERCC1rs2298881 polymorphism is associated with risk of glioma in codominant, dominant, and recessive models, especially in males, smokers, and high-grade glioma cases.
The results of our meta-analysis strongly suggested that the ERCC1rs3212986 polymorphism was associated with a higher susceptibility to glioma, particularly in the Chinese population.
For ERCC1C8092A (dbSNP: rs3212986, C>A), the combined results show that carriers of the AA genotype may be associated with a higher risk of adult glioma than carriers of the CA and CC genotypes.
Overall, ERCC1C8092A polymorphism was associated with the risk of glioma (AA vs. CC: OR = 1.29, 95%CI: 1.07-1.55, P = 0.01; recessive model: OR = 1.29; 95% CI: 1.07-1.55, P = 0.01).
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.
Using a stringent P < 0.001, glioma survival was associated with ERCC1C8092A [hazard ratio (HR), 0.72; 95% confidence limits (95% CL), 0.60-0.86; P = 0.0004] and GSTT1 deletion (HR, 1.64; 95% CL, 1.25-2.16; P = 0.0004); glioblastoma patients with elevated IgE had 9 months longer survival than those with normal or borderline IgE levels (HR, 0.62; 95% CL, 0.47-0.82; P = 0.0007), and EGFR expression in anaplastic astrocytoma was associated with nearly 3-fold poorer survival (HR, 2.97; 95% CL, 1.70-5.19; P = 0.0001).
We found that SNPs rs3212986 (odds ratio [OR] = 1.35 (1.08-1.68), P = .008), rs13181 (OR = 1.18 (1.06-1.31), P = .002), and rs25487 (OR = 1.12 (1.03-1.22), P = .007) in DNA repair genes ERCC1, ERCC2 (XPD), and XRCC1 may increase the risk of glioma, while polymorphisms rs1136410 (OR = 0.78 (0.68-0.89), P = .0004) and rs12917 (OR = 0.84 (0.73-0.96), P = .01) in PARP1(ADPRT) and MGMT are associated with decreased susceptibility to glioma.
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 conclusion, we observed that the XPD 751Gln/Gln genotype is associated with glioma susceptibility, and ERCC1 118 T/T and XPD 751Gln/Gln genotypes confer a significantly better prognosis.