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Association between DNA repair gene polymorphisms and risk of glioma: A systematic review and meta-analysis
Authors:Maral Adel Fahmideh  Judith Schwartzbaum  Paolo Frumento  Maria Feychting
Affiliation:Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden (M.A.F., M.F.); Division of Epidemiology, College of Public Health, The Ohio State University, Columbus, Ohio (J.S.); Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden (P.F.)
Abstract:

Background

Association studies of germline DNA repair single nucleotide polymorphisms (SNPs) and glioma risk have yielded inconclusive results. We therefore performed a systematic review and meta-analysis of studies investigating this association.

Methods

We identified 27 eligible studies investigating 105 SNPs in 42 DNA repair genes. Of these, 10 SNPs in 7 genes were analyzed in at least 4 studies and were therefore included in our meta-analysis. The meta-analysis was performed for homozygote comparison, heterozygote comparison, and dominant and recessive models by applying a fixed- or random-effects model. The funnel and forest plots were created using RevMan software.

Results

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. No evidence of significant associations between ERCC2 rs1799793, OGG1 rs1052133, XRCC1 rs25489, XRCC1 rs1799782, or XRCC3 rs861539 and risk of glioma was observed.

Conclusion

This study provides evidence that DNA repair genes ERCC1, ERCC2, and XRCC1 might be low-penetrance glioma-risk genes, while MGMT and PARP1 polymorphisms may confer protection against glioma.
Keywords:brain neoplasm   DNA repair   glioma   meta-analysis   single nucleotide polymorphism
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