Tumor Biology

, Volume 34, Issue 5, pp 2827–2834 | Cite as

DNA repair gene XRCC3 Thr241Met polymorphism and hepatocellular carcinoma risk

  • Chenyang Duan
  • Wanli Zhang
  • Jiangfeng Lu
  • Huawen Wu
  • Mengying Liu
  • Wentao Zhu
Research Article

Abstract

The DNA repair genes have been indicated as candidates in the risk of hepatocellular carcinoma (HCC). Published data on the association between X-ray repair cross-complementing group 3 (XRCC3), a critical member of the DNA repair genes, and HCC risk were contradictory. The aim of this meta-analysis was to assess the effect of XRCC3 Thr241Met polymorphism on HCC risk by pooling available data from published case–control studies. We calculated the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) to estimate the effect. Based on the inclusion criteria, six individual studies with 2,288 cases and 3,170 controls were included into our study. Overall, significant association between the XRCC3 Thr241Met variant and HCC risk was observed under the following contrast models (ORMet vs. Thr = 1.68, 95 %CI 1.08–2.62; ORMetMet vs. ThrThr = 5.54, 95 %CI 3.09–9.94; ORMetMet vs. ThrThr + ThrMet = 5.70, 95 % CI 4.24–7.64). Besides, the pooled ORs indicated that the XRCC3 Thr241Met polymorphism exerted risk effect on the HCC pathogenesis among Asians. Additionally, when stratifying by the status of smoking and hepatitis B virus infection, the XRCC3 Thr241Met variant was significantly associated with HCC risk among the HBsAg (+) individuals but not the HBsAg (−) individuals, smokers, and non-smokers. The present meta-analysis suggests that the XRCC3 Thr241Met polymorphism is an independent risk factor for HCC, particularly among Asians and the HBsAg (+) individuals.

Keywords

Hepatocellular carcinoma X-ray repair cross-complementing group 3 Polymorphism Meta-analysis 

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Allen J, Venook A. Hepatocellular carcinoma: epidemic and treatment. Curr Oncol Rep. 2004;6:177–83.CrossRefPubMedGoogle Scholar
  3. 3.
    Tong CY, Khan R, Beeching NJ, Tariq WU, Hart CA, Ahmad N, et al. The occurrence of hepatitis B and C viruses in Pakistani patients with chronic liver disease and hepatocellular carcinoma. Epidemiol Infect. 1996;117:327–32.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Stroffolini T. Etiological factor of hepatocellular carcinoma in Italy. Minerva Gastroenterol Dietol. 2005;51:1–5.PubMedGoogle Scholar
  5. 5.
    Naugler WE, Schwartz JM. Hepatocellular carcinoma. Dis Mon. 2008;54:432–44.CrossRefPubMedGoogle Scholar
  6. 6.
    Sanyal AJ, Yoon SK, Lencioni R. The etiology of hepatocellular carcinoma and consequences for treatment. Oncologist. 2010;15 Suppl 4:14–22.CrossRefPubMedGoogle Scholar
  7. 7.
    Bose S, Tripathi DM, Sukriti, Sakhuja P, Kazim SN, Sarin SK. Genetic polymorphisms of CYP2E1 and DNA repair genes HOGG1 and XRCC1: association with hepatitis B related advanced liver disease and cancer. Gene. 2013;519:231–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Schneider J, Classen V, Helmig S. XRCC1 polymorphism and lung cancer risk. Expert Rev Mol Diagn. 2008;8:761–80.CrossRefPubMedGoogle Scholar
  9. 9.
    Nissar S, Lone TA, Banday MZ, Rasool R, Chowdri NA, Parray FQ, et al. Arg399Gln polymorphism of XRCC1 gene and risk of colorectal cancer in Kashmir: a case control study. Oncol Lett. 2013;5:959–63.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Romanowicz-Makowska H, Brys M, Forma E, Maciejczyk R, Polac I, Samulak D, et al. Single nucleotide polymorphism (SNP) Thr241Met in the XRCC3 gene and breast cancer risk in Polish women. Pol J Pathol. 2012;63:121–5.PubMedGoogle Scholar
  11. 11.
    Gresner P, Gromadzinska J, Polanska K, Twardowska E, Jurewicz J, Wasowicz W. Genetic variability of Xrcc3 and Rad51 modulates the risk of head and neck cancer. Gene. 2012;504:166–74.CrossRefPubMedGoogle Scholar
  12. 12.
    Vral A, Willems P, Claes K, Poppe B, Perletti G, Thierens H. Combined effect of polymorphisms in Rad51 and Xrcc3 on breast cancer risk and chromosomal radiosensitivity. Mol Med Rep. 2011;4:901–12.PubMedGoogle Scholar
  13. 13.
    Xu YH, Gu LP, Sun YJ, Cheng BJ, Lu S. No significant association between the XRCC3 Thr241Met polymorphism and lung cancer risk: a meta-analysis. Tumour Biol. 2013;34:865–74.CrossRefPubMedGoogle Scholar
  14. 14.
    Gulnaz A, Sayyed AH, Amin F, Khan A, Aslam MA, Shaikh RS, et al. Association of XRCC1, XRCC3, and XPD genetic polymorphism with an increased risk of hepatocellular carcinoma because of the hepatitis B and C virus. Eur J Gastroenterol Hepatol. 2013;25:166–79.CrossRefPubMedGoogle Scholar
  15. 15.
    Han X, Xing Q, Li Y, Sun J, Ji H, Huazheng P, et al. Study on the DNA repair gene XRCC1 and XRCC3 polymorphism in prediction and prognosis of hepatocellular carcinoma risk. Hepatogastroenterology. 2012;59.Google Scholar
  16. 16.
    Long XD, Ma Y, de Qu Y, Liu YG, Huang ZQ, Huang YZ, et al. The polymorphism of XRCC3 codon 241 and AFB1-related hepatocellular carcinoma in Guangxi population, China. Ann Epidemiol. 2008;18:572–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Zeng X, Liu S, Yu H, Ji L, Li L, Huang J, et al. DNA repair capacity, DNA-strand break repair gene polymorphisms, and the incidence of hepatocellular carcinoma in southwestern Guangxi of China. DNA Cell Biol. 2012;31:1384–91.PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Long XD, Ma Y, Deng ZL, Huang YZ, Wei NB. Association of the Thr241Met polymorphism of DNA repair gene XRCC3 with genetic susceptibility to AFB1-related hepatocellular carcinoma in Guangxi population. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008;25:268–71 [Article in Chinese].PubMedGoogle Scholar
  19. 19.
    Cochran WG. The comparison of percentages in matched samples. Biometrika. 1950;37:256–66.CrossRefPubMedGoogle Scholar
  20. 20.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMedGoogle Scholar
  22. 22.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.PubMedGoogle Scholar
  23. 23.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Stuck AE, Rubenstein LZ, Wieland D. Bias in meta-analysis detected by a simple, graphical test. Asymmetry detected in funnel plot was probably due to true heterogeneity. BMJ. 1998;316:469. author reply 70–1.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Liu W. The relation between genetic polymorphism of DNA repair genes XRCC3 and XRCC4 in susceptibility to primary hepatocellular carcinoma. Fujian Med Univ. 2010. [Article in Chinese].Google Scholar
  26. 26.
    Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science. 1996;273:1516–7.CrossRefPubMedGoogle Scholar
  27. 27.
    Hamdy MS, El-Haddad AM, Bahaa El-Din NM, Makhlouf MM, Abdel-Hamid SM. RAD51 and XRCC3 gene polymorphisms and the risk of developing acute myeloid leukemia. J Investig Med. 2011;59:1124–30.PubMedGoogle Scholar
  28. 28.
    Krupa R, Sliwinski T, Wisniewska-Jarosinska M, Chojnacki J, Wasylecka M, Dziki L, et al. Polymorphisms in RAD51, XRCC2 and XRCC3 genes of the homologous recombination repair in colorectal cancer—a case control study. Mol Biol Rep. 2011;38:2849–54.PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Zhan P, Wang Q, Qian Q, Yu LK. XRCC3 Thr241Met gene polymorphisms and lung cancer risk: a meta-analysis. J Exp Clin Cancer Res. 2013;32:1.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Silva SN, Tomar M, Paulo C, Gomes BC, Azevedo AP, Teixeira V, et al. Breast cancer risk and common single nucleotide polymorphisms in homologous recombination DNA repair pathway genes XRCC2, XRCC3, NBS1 and RAD51. Cancer Epidemiol. 2010;34:85–92.CrossRefPubMedGoogle Scholar
  31. 31.
    Yu MC, Yuan JM. Environmental factors and risk for hepatocellular carcinoma. Gastroenterology. 2004;127:S72–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Chuang SC, La Vecchia C, Boffetta P. Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Lett. 2009;286:9–14.CrossRefPubMedGoogle Scholar
  33. 33.
    Jiang DK, Sun J, Cao G, Liu Y, Lin D, Gao YZ, et al. Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Nat Genet. 2013;45:72–5.PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Wild CP, Montesano R. A model of interaction: aflatoxins and hepatitis viruses in liver cancer aetiology and prevention. Cancer Lett. 2009;286:22–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Yoon YJ, Chang HY, Ahn SH, Kim JK, Park YK, Kang DR, et al. MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. Carcinogenesis. 2008;29:1192–6.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Chenyang Duan
    • 1
  • Wanli Zhang
    • 2
  • Jiangfeng Lu
    • 3
  • Huawen Wu
    • 4
  • Mengying Liu
    • 5
  • Wentao Zhu
    • 6
  1. 1.Company Five of Cadet Brigade, Clinical Department of MedicineThird Military Medical UniversityChongqingChina
  2. 2.Cancer Center, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Binzhou Medical UniversityBinzhouChina
  4. 4.Institute of Electronic Computing TechnologyChina Academy of Railway ScienceBeijingChina
  5. 5.Company Two of Cadet Brigade, Clinical Department of MedicineThird Military Medical UniversityChongqingChina
  6. 6.Department of Orthopaedics, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Personalised recommendations