DNA Repair Gene ERCC1 and XPD Polymorphisms Predict Glioma Susceptibility and Prognosis

  • Chen, Da-Qing (The Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Yao, Dong-Xiao (The Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Zhao, Hong-Yang (The Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Yang, Shu-Juan (West China School of Public Health, Sichuan University)
  • Published : 2012.06.30


Aims: We conducted a case-control study in a Chinese population to clarify the association between polymorphisms in ERCC1 and XPD and susceptibility and survival of glioma. Methods: A total of 393 cases and 410 controls were selected from March 2007 to December 2011. Genotyping of ERCC1 and XPD was conducted by TaqMan assays using the ABI Prism 7911HT Sequence Detection System. All analyses were performed using the STATA statistical package. Results: Polymorphisms in ERCC1 118C/T, ERCC1 8092C/A and XPD Asp312Asn showed no statistically significant difference between glioma cases and controls. However, individuals with the XPD 751Gln/Gln genotype had an increased risk of developing glioma compared with those with the Lys/Lys genotype (adjusted OR=1.64, 95% CI: 1.06-2.89). The ERCC1 118T/T genotype was associated with significantly higher median survival than the ERCC1 C/C genotype (HR=0.67, 95%CI=0.35-0.96). In addition, individuals with XPD 751Gln/Gln had a lower median survival time than XPD Lys/Lys carriers (HR=0.54, 95%CI=0.37-0.93). Conclusion: 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.


  1. Altaha R, Liang X, Yu JJ, et al (2004). Excision repair cross complementing-group 1: gene expression and platinum resistance. Int J Mol Med, 14, 959-70.
  2. Batchelor TT, Betensky RA, Esposito JM, et al (2004). Agedependent prognostic effects of genetic alterations in glioblastoma. Clin Cancer Res, 10, 228-33.
  3. Benhamou S, Sarasin A (2002). ERCC2/XPD gene polymorphisms and cancer risk. Mutagenesis, 17, 463-9.
  4. Benhamou S, Sarasin A (2005). ERCC2 /XPD gene polymorphisms and lung cancer: a Huge review. Am J Epidemiol, 161, 1-14.
  5. Braithwaite E, Wu X, Wang Z (1999). Repair of DNA lesions: mechanisms and relative repair efficiencies. Mutat Res, 424, 207-19.
  6. Chen HY, Shao CJ, Shi HL, et al (2007). Single nucleotide polymorphisms and expression of ERCC1 and ERCC2 visa- vis chemotherapy drug cytotoxicity in human glioma. J Neurooncol, 82, 257-62.
  7. Coin F, Bergmann E, Tremeau-Bravard A, et al (1999). Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair the transcription function of TFIIH. Embo J, 18, 1357-66.
  8. de Laat WL, Jaspers NG, Hoeijmakers JH(1999). Molecular mechanism of nucleotide excision repair. Genes Dev, 13, 768-85.
  9. Flejter WL, McDaniel LD, Johns D, et al (1992). Correction of xeroderma pigmentosum complementation group D mutant cell phenotypes by chromosome and gene transfer: involvement of the human ERCC2 DNA repair gene. Proc Natl Acad Sci USA, 89, 261-5.
  10. Goyal S, Parikh RR, Green C, et al (2010). Clinicopathologic significance of excision repair cross-complementation 1 expression in patients treated with breast-conserving surgery and radiation therapy. Int J Radiat Oncol Biol Phys, 76, 679-84.
  11. Hayes M, Lan C, Yan J, et al (2011). ERCC1 expression and outcomes in head and neck cancer treated with concurrent cisplatin and radiation. Anticancer Res, 31, 4135-9.
  12. Houillier C, Lejeune J, Benouaich-Amiel A, et al(2006). Prognostic impact of molecular markers in a series of 220 primary glioblastomas. Cancer, 106, 2218-23.
  13. Hu XB, Feng Z, Fan YC, et al (2011). Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to glioma. Asian Pac J Cancer Prev, 12, 2981-4.
  14. Jensen NF, Smith DH, Nygard SB, et al (2012). Predictive biomarkers with potential of converting conventional chemotherapy to targeted therapy in patients with metastatic colorectal cancer. Scand J Gastroenterol, 47, 340-55.
  15. Kiuru A, LindholmC, Heinavaara S, et al (2008). XRCC1 and XRCC3 variants and risk of glioma and meningioma. J Neurooncol, 88, 135-142.
  16. Kuwabara K, Kumamoto K, Ishibashi K, et al (2011). The Relationship between the efficacy of mFOLFOX6 treatment and the expression of TS, DPD, TP, and ERCC-1 in unresectable colorectal cancer. Gan To Kagaku Ryoho, 38, 2224-7.
  17. Leichman L, Lawrence D, Leichman CG, et al (2006). Expression of genes related to activity of oxaliplatin and 5-fluorouracil in endoscopic biopsies of primary esophageal cancer in patients receiving oxaliplatin, 5-flourouracil and radiation: characterization and exploratory analysis with survival. J Chemother, 18, 514-24.
  18. Leng XF, Chen MW, Xian L, et al (2012). Combined analysis of mRNA expression of ERCC1, BAG-1, BRCA1, RRM1 and TUBB3 to predict prognosis in patients with non-small cell lung cancer who received adjuvant chemotherapy. J Exp Clin Cancer Res, 31, 25.
  19. Liao WY, Shih JY, Chang GC, et al (2012). Genetic polymorphism of XRCC1 Arg399Gln is associated with survival in nonsmall- cell lung cancer patients treated with gemcitabine/ platinum. J Thorac Oncol, 7, 973-81.
  20. Lindahl T, Karran P, Wood RD (1997). DNA excision repair pathways. Curr Opin Genet Dev, 7, 158-69.
  21. Liu Y, Scheurer ME, El-Zein R, et al (2009). Association and interactions between DNA repair gene polymorphisms and adult glioma. Cancer Epidemiol Biomarkers Prev, 18, 204-14.
  22. Milovic-Kovacevic M, Srdic-Rajic T, Radulovic S, et al(2011). Expression of ERCC1 protein in biopsy specimen predicts survival in advanced ovarian cancer patients treated with platinum-based chemotherapy. J BUON, 16, 708-14.
  23. Ohgaki H, Dessen P, Jourde B, et al(2004). Genetic pathways to glioblastoma: A population-based study. Cancer Res, 64, 6892-9.
  24. Rajaraman P, Hutchinson A, Wichner S, et al (2010). DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic neuroma. Neuro Oncol, 12, 37-48.
  25. Rich JN, Hans C, Jones B, et al (2005). Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res, 65, 4051-508.
  26. Sung P, Bailly V, Weber C, et al (1993). Human xeroderma pigmentosum group D gene encodes a DNA helicase. Nature, 365, 852-5.
  27. Wang LE, Bondy ML, Shen H, et al (2004). Polymorphisms of DNA repair genes and risk of glioma. Cancer Res, 64, 5560-3.
  28. Weeda G, Hoeijmakers JH(1993). Genetic analysis of nucleotide excision repair in mammalian cells. Semin Cancer Biol, 4, 105-17.
  29. Wrensch M, Kelsey KT, Liu M, et al (2005). ERCC1 and ERCC2 polymorphisms and adult glioma. Neuro Oncol, 7, 495-507.
  30. Yan L, Shu-Ying Y, Shan K, et al (2012). Association between polymorphisms of ERCC1 and survival in epithelial ovarian cancer patients with chemotherapy. Pharmacogenomics, 13, 419-27.
  31. Yosunkaya E, Kucukyuruk B, Onaran I, et al (2010). Glioma risk associateswith polymorphisms of DNA repair genes, XRCC1 and PARP1. Br J Neurosurg, 24, 561-5.
  32. Zhang N, Lin LY, Zhu LL, et al (2012). ERCC1 polymorphisms and risk of adult glioma in a Chinese population: a hospitalbased case-control study. Cancer Invest, 30, 199-202.
  33. Zhou K, Liu Y, Zhang H, et al (2009). XRCC3 haplotypes and risk of gliomas in a Chinese population: a hospital-based case-control study. Int J Cancer, 124, 2948-53.
  34. Zhou LQ, Ma Z, Shi XF, et al (2011). Polymorphisms of DNA repair gene XRCC1 and risk of glioma: a case-control study in Southern China. Asian Pac J Cancer Prev, 12, 2547-50.

Cited by

  1. Xeroderma Pigmentosum Complementation Group F Polymorphisms Influence Risk of Glioma vol.14, pp.7, 2013,
  2. XPD Lys751Gln and Asp312Asn Polymorphisms and Susceptibility to Skin Cancer: A Meta-Analysis of 17 Case-control Studies vol.15, pp.16, 2014,
  3. Comparison of Linear Accelerator and Helical Tomotherapy Plans for Glioblastoma Multiforme Patients vol.15, pp.18, 2014,
  4. Increased Argonaute 2 Expression in Gliomas and its Association with Tumor Progression and Poor Prognosis vol.15, pp.9, 2014,
  5. Association between DNA repair gene polymorphisms and risk of glioma: A systematic review and meta-analysis vol.16, pp.6, 2014,
  6. DNA repair mechanisms and Toxoplasma gondii infection vol.196, pp.1, 2014,
  7. A pooled analysis of the ERCC2 Asp312Asn polymorphism and esophageal cancer susceptibility vol.35, pp.4, 2014,
  8. Association between ERCC1 C8092A and ERCC2 K751Q polymorphisms and risk of adult glioma: a meta-analysis vol.35, pp.4, 2014,
  9. DNA repair gene ERCC1 polymorphisms may contribute to the risk of glioma vol.35, pp.5, 2014,
  10. Association of single-nucleotide polymorphisms in ERCC1 and ERCC2 with glioma risk vol.35, pp.8, 2014,
  11. Association of ERCC1 C8092A and ERCC2 Lys751Gln Polymorphisms with the Risk of Glioma: A Meta-Analysis vol.9, pp.4, 2014,
  12. A Comprehensive Analysis of Influence ERCC Polymorphisms Confer on the Development of Brain Tumors vol.53, pp.4, 2016,
  13. Polymorphisms in DNA Repair Gene and Susceptibility to Glioma: A Systematic Review and Meta-Analysis Based on 33 Studies with 15 SNPs in 9 Genes vol.37, pp.2, 2017,
  14. Association between common polymorphisms in ERCC gene and glioma risk vol.96, pp.20, 2017,