Abstract
While the ERCC1 C8092A and ERCC2 K751Q polymorphisms have received much attention for their potential associations with adult glioma risk, inferences from such studies are hindered by their limited statistical power and conflicting results. The aim of this meta-analysis is to provide a relatively comprehensive account of the association between these two polymorphisms and adult glioma risk. A literature search for eligible studies published before September 1, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and CNKI databases. Pooled odds ratios (ORs) with their corresponding 95 % confidence intervals (95 % CIs) were used to evaluate the strength of the association under a fixed or random effect model according to heterogeneity test results. All analyses were performed using STATA software, version 12.0. Ten case–control studies were included in this meta-analysis, with a total of 5,843 adult glioma patients and 8,139 healthy controls. For ERCC1 C8092A (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. Stratified analyses show that the magnitude of the effect was especially significant among Asians, indicating ethnicity differences in adult glioma susceptibility. For ERCC2 K751Q (dbSNP: rs13181, A>C), the pooled ORs were not significant in the overall population, although all of the ORs were greater than 1. However, Asians seem to be significantly more susceptible to adult glioma than Caucasians. The results of this meta-analysis indicate that the AA genotype of ERCC1 C8092A may be associated with a higher risk of adult glioma than the CA and CC genotypes and that the risk allele of ERCC2 K751Q confers a significant susceptibility to adult glioma, especially in Asian populations. These polymorphisms may be used along with other genetic markers to identify individuals at high risk for adult glioma.
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Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M. Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol. 2006;2:494–503. quiz 1 p following 16.
Dolecek TA, Propp JM, Stroup NE, Kruchko C. CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the united states in 2005–2009. Neuro Oncol. 2012;14 Suppl 5:v1–v49.
Bellail AC, Hunter SB, Brat DJ, Tan C, Van Meir EG. Microregional extracellular matrix heterogeneity in brain modulates glioma cell invasion. Int J Biochem Cell Biol. 2004;36:1046–69.
Plascak JJ, Fisher JL. Area-based socioeconomic position and adult glioma: a hierarchical analysis of surveillance epidemiology and end results data. PLoS One. 2013;8:e60910.
Perera FP. Environment and cancer: who are susceptible? Science. 1997;278:1068–73.
Burcham PC. Internal hazards: baseline DNA damage by endogenous products of normal metabolism. Mutat Res. 1999;443:11–36.
Liu BH, Yu FY, Wu TS, Li SY, Su MC, et al. Evaluation of genotoxic risk and oxidative DNA damage in mammalian cells exposed to mycotoxins, patulin and citrinin. Toxicol Appl Pharmacol. 2003;191:255–63.
Little JB. Genomic instability and radiation. J Radiol Prot. 2003;23:173–81.
Ames BN. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat Res. 2001;475:7–20.
Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA. DNA repair pathways as targets for cancer therapy. Nat Rev Cancer. 2008;8:193–204.
Goode EL, Ulrich CM, Potter JD. Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev. 2002;11:1513–30.
Wood RD, Mitchell M, Lindahl T. Human DNA repair genes, 2005. Mutat Res. 2005;577:275–83.
Smith JS, Tachibana I, Pohl U, Lee HK, Thanarajasingam U, et al. A transcript map of the chromosome 19q-arm glioma tumor suppressor region. Genomics. 2000;64:44–50.
Garcia-Closas M, Malats N, Real FX, Welch R, Kogevinas M, et al. Genetic variation in the nucleotide excision repair pathway and bladder cancer risk. Cancer Epidemiol Biomarkers Prev. 2006;15:536–42.
Munafo MR, Flint J. Meta-analysis of genetic association studies. Trends Genet. 2004;20:439–44.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.
Little J, Higgins JP, Ioannidis JP, Moher D, Gagnon F, et al. Strengthening the Reporting of Genetic Association studies (STREGA): an extension of the STROBE statement. Hum Genet. 2009;125:131–51.
Stang A. Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol. 2010;25:603–5.
Jackson D, White IR, Riley RD. Quantifying the impact of between-study heterogeneity in multivariate meta-analyses. Stat Med. 2012;31:3805–20.
Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.
Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA. 2006;295:676–80.
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.
Chen P, Wiencke J, Aldape K, Kesler-Diaz A, Miike R, et al. Association of an ercc1 polymorphism with adult-onset glioma. Cancer Epidemiol Biomarkers Prev. 2000;9:843–7.
Wrensch M, Kelsey KT, Liu M, Miike R, Moghadassi M, et al. ERCC1 and ERCC2 polymorphisms and adult glioma. Neuro Oncol. 2005;7:495–507.
Liu Y, Scheurer ME, El-Zein R, Cao Y, Do KA, et al. Association and interactions between DNA repair gene polymorphisms and adult glioma. Cancer Epidemiol Biomarkers Prev. 2009;18:204–14.
McKean-Cowdin R, Barnholtz-Sloan J, Inskip PD, Ruder AM, Butler M, et al. Associations between polymorphisms in DNA repair genes and glioblastoma. Cancer Epidemiol Biomarkers Prev. 2009;18:1118–26.
Chen DQ, Yao DX, Zhao HY, Yang SJ. DNA repair gene ERCC1 and XPD polymorphisms predict glioma susceptibility and prognosis. Asian Pac J Cancer Prev. 2012;13:2791–4.
Zhang N, Lin LY, Zhu LL, Wu F, Wen H, et al. ERCC1 polymorphisms and risk of adult glioma in a Chinese population: a hospital-based case–control study. Cancer Invest. 2012;30:199–202.
Pan WR, Li G, Guan JH. Polymorphisms in DNA repair genes and susceptibility to glioma in a Chinese population. Int J Mol Sci. 2013;14:3314–24.
Caggana M, Kilgallen J, Conroy JM, Wiencke JK, Kelsey KT, et al. Associations between ERCC2 polymorphisms and gliomas. Cancer Epidemiol Biomarkers Prev. 2001;10:355–60.
Rajaraman P, Hutchinson A, Wichner S, Black PM, Fine HA, et al. DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic neuroma. Neuro Oncol. 2010;12:37–48.
Luo KQ, Mu SQ, Wu ZX, Shi YN, Peng JC. Polymorphisms in DNA repair genes and risk of glioma and meningioma. Asian Pac J Cancer Prev. 2013;14:449–52.
Vanan I, Dong Z, Tosti E, Warshaw G, Symons M, et al. Role of a DNA damage checkpoint pathway in ionizing radiation-induced glioblastoma cell migration and invasion. Cell Mol Neurobiol. 2012;32:1199–208.
Mahaney BL, Meek K, Lees-Miller SP. Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining. Biochem J. 2009;417:639–50.
Hoeijmakers JH. DNA damage, aging, and cancer. N Engl J Med. 2009;361:1475–85.
Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, et al. Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet. 2009;41:899–904.
Rajaraman P, Melin BS, Wang Z, McKean-Cowdin R, Michaud DS, et al. Genome-wide association study of glioma and meta-analysis. Hum Genet. 2012;131:1877–88.
Lai R, Crevier L, Thabane L. Genetic polymorphisms of glutathione S-transferases and the risk of adult brain tumors: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2005;14:1784–90.
Tan D, Xu J, Li Y, Lai R. Association between +61g polymorphism of the EGF gene and glioma risk in different ethnicities: a meta-analysis. Tohoku J Exp Med. 2010;222:229–35.
Jacobs DI, Bracken MB. Association between XRCC1 polymorphism 399 g→a and glioma among Caucasians: a systematic review and meta-analysis. BMC Med Genet. 2012;13:97.
He F, Xia Y, Liu H, Li J, Wang C. P53 codon 72 arg/pro polymorphism and glioma risk: an updated meta-analysis. Tumour Biol. 2013;34:3121–30.
Lu Q, Dai D, Zhao W, Wang L, Yue Z, et al. Association between mthfr 677c>t polymorphism and risk of gliomas: evidence from a meta-analysis. Tumour Biol. 2013;34:2801–7.
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This work was supported by the grants from Clinical Application of Molecular Diagnostic Techniques in Personalized Brain Tumor Therapy (W2012FZ009), Development Center for Medical Science and Technollgy, Ministry of Health ,P.R.China.
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Xu, Z., Ma, W., Gao, L. et al. Association between ERCC1 C8092A and ERCC2 K751Q polymorphisms and risk of adult glioma: a meta-analysis. Tumor Biol. 35, 3211–3221 (2014). https://doi.org/10.1007/s13277-013-1420-9
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DOI: https://doi.org/10.1007/s13277-013-1420-9