Abstract
The X-ray repair cross-complementing group 1 (XRCC1) gene, one of over 20 genes that participate in the base excision repair pathway, is thought to account for differences in susceptibility to hepatocellular carcinoma. To assess the relationship between the XRCC1 Arg399Gln polymorphism and the risk of hepatocellular carcinoma (HCC), we performed a meta-analysis. All the relevant studies were extracted from PubMed, Embase, the Chinese biomedicine databases, the Chinese national knowledge infrastructure, and the Wanfang databases (prior to August 2012). The meta-analysis was performed using all eligible studies, which covered a total of 2,554 cases and 3,320 controls, to examine the association between XRCC1 Arg399Gln polymorphism and the risk of HCC. Our analysis suggested that the variant genotypes of the XRCC1 Arg399Gln gene were associated with a significantly increased risk of HCC in a co-dominant model (Arg/Gln vs. Arg/Arg, odd ratios [OR] 1.39, 95 % confidence interval [CI] 1.08–1.79; Gln/Gln vs. Arg/Arg, OR 1.26, 95 % CI 1.04–1.52) and a dominant model (Arg/Gln + Gln/Gln vs. Arg/Arg OR 1.36, 95 % CI 1.07–1.72), whereas no association was observed in the recessive model (Gln/Gln vs. Arg/Gln + Arg/Arg, OR 1.05, 95 % CI 0.91–1.21). The results of the subgroup analysis by ethnicity indicated that the XRCC1 Arg399Gln polymorphism was associated with increased risk of HCC in Asian populations using the co-dominant model (Arg/Gln vs. Arg/Arg, OR 1.41, 95 % CI 1.06–1.87) and the dominant model (Gln/Gln vs. Arg/Gln + Arg/Arg, OR 1.35, 95 % CI 1.03–1.76). Our analysis provides evidence that the XRCC1 Arg399Gln polymorphism may be associated with a higher risk of HCC, especially among Asian populations.
Similar content being viewed by others
References
Ruggeri M (2012) Hepatocellular carcinoma: cost-effectiveness of screening. A systematic review. Risk Manag Healthc Policy 5:49–54
Kirk GD, Lesi OA, Mendy M, Akano AO, Sam O, Goedert JJ, Hainaut P, Hall AJ, Whittle H, Montesano R (2004) The Gambia liver cancer study: infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa. Hepatology 39(1):211–219
Wu HC, Santella R (2012) The role of aflatoxins in hepatocellular carcinoma. Hepat Mon 12(10):e7238
Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS (2005) Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J Hepatol 42(2):218–224
Jiang DK, Sun J, Cao G, Liu Y, Lin D, Gao YZ, Ren WH, Long XD, Zhang H, Ma XP et al (2013) Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma. Nat Genet 45(1):72–75
Al-Qahtani A, Al-Anazi M, Viswan NA, Khalaf N, Abdo AA, Sanai FM, Al-Ashgar H, Al-Ahdal M (2012) Role of single nucleotide polymorphisms of KIF1B gene in HBV-associated viral hepatitis. PLoS ONE 7(9):e45128
Yuan T, Wei J, Luo J, Liu M, Deng S, Chen P (2012) Polymorphisms of base-excision repair genes hOGG1 326cys and XRCC1 280His increase hepatocellular carcinoma risk. Dig Dis Sci 57(9):2451–2457
Li S, Qian J, Yang Y, Zhao W, Dai J, Bei JX, Foo JN, McLaren PJ, Li Z, Yang J et al (2012) GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers. PLoS Genet 8(7):e1002791
Smith TR, Miller MS, Lohman K, Lange EM, Case LD, Mohrenweiser HW, Hu JJ (2003) Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer Lett 190(2):183–190
Li Y, Liu F, Tan SQ, Wang Y, Li SW (2012) X-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms and cervical cancer risk: a huge systematic review and meta-analysis. PLoS ONE 7(9):e44441
Duman N, Aktan M, Ozturk S, Palanduz S, Cakiris A, Ustek D, Ozbek U, Nalcaci M, Cefle K (2012) Investigation of Arg399Gln and Arg194Trp polymorphisms of the XRCC1 (X-ray cross-complementing group 1) gene and its correlation to sister chromatid exchange frequency in patients with chronic lymphocytic leukemia. Genet Test Mol Biomarkers 16(4):287–291
Bianchino G, Cittadini A, Grieco V, Traficante A, Zupa A, Improta G, Aieta M, Sgambato A (2011) Polymorphisms of the CYP1A1, CYP2E1 and XRCC1 genes and cancer risk in a Southern Italian population: a case-control study. Anticancer Res 31(4):1359–1365
Liu F, Li B, Wei Y, Yan L, Wen T, Zhao J, Xu M (2011) XRCC1 genetic polymorphism Arg399Gln and hepatocellular carcinoma risk: a meta-analysis. Liver Int 31(6):802–809
Xie T, Wang ZG, Zhang JL, Liu H (2012) X-ray repair cross-complementing group 1 polymorphisms and hepatocellular carcinoma: a meta-analysis. World J gastroenterol 18(31):4207–4214
Duan WH, Zhu ZY, Liu JG, Dong MS, Chen JZ, Liu QD, Xie Y, Sun TY, Gao ZF, Zhou NX (2012) XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma risk in the Chinese Han population: a meta-analysis. Asian Pac J Cancer Prev 13(8):3601–3604
Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188
Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748
Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50(4):1088–1101
Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634
Xu L (2003) A case-control study on association between genetic polymorphisms of DNA repair gene and primary liver cancer susceptibility. http://dwanfangdatacomcn/Thesis_Y556061aspx (article in Chinese). Accessed 15 June 2004
Long X, Ma Y, Wei Y, Deng Z (2004) Polymorphism of DNA repair gene XRCC1 and risk of hepatocellular carcinoma. J Guangxi Med Univ 21(3):313–315 (article in Chinese)
Yang J, Han Y, Zheng S (2004) Influence of human XRCC1-399 nucleotide polymorphism primary hepatocytic carcinoma. Tumor 24(2):322–324 (article in Chinese)
Zt L (2005) The association between DNA repair gene polymorphism and aberrant methylation and hepatocelluar carcinoma. Available at Sun Yat-sen University Libraries (article in Chinese). Accession number: TN14058. Accessed 25 May 2005
Chen CC, Yang SY, Liu CJ, Lin CL, Liaw YF, Lin SM, Lee SD, Chen PJ, Chen CJ, Yu MW (2005) Association of cytokine and DNA repair gene polymorphisms with hepatitis B-related hepatocellular carcinoma. Int J Epidemiol 34(6):1310–1318
Kirk GD, Turner PC, Gong Y, Lesi OA, Mendy M, Goedert JJ, Hall AJ, Whittle H, Hainaut P, Montesano R et al (2005) Hepatocellular carcinoma and polymorphisms in carcinogen-metabolizing and DNA repair enzymes in a population with aflatoxin exposure and hepatitis B virus endemicity. Cancer Epidemiol Biomarkers Prev 14(2):373–379
Borentain P, Gerolami V, Ananian P, Garcia S, Noundou A, Botta-Fridlund D, Le Treut YP, Berge-Lefranc JL, Gerolami R (2007) DNA-repair and carcinogen-metabolising enzymes genetic polymorphisms as an independent risk factor for hepatocellular carcinoma in Caucasian liver-transplanted patients. Eur J Cancer 43(17):2479–2486
Ren X, Wang D, Li Z, Xin Y, Yin J, Zhang B, Ding H, Li N (2008) Study on the relationship between gene XRCC1 codon 399 single nucleotide polymorphisms and primary hepatic carcinoma in Han nationality. Chin J Clin Hepatol 24(5):361–365 (article in Chinese)
SU H (2008) A case-control study on association between genetic polymorphisms of DNA repair and hepatic cell cancer susceptibility. Available at http://dwanfangdatacomcn/Thesis_Y1300729aspx (article in Chinese)
Kiran M, Saxena R, Chawla YK, Kaur J (2009) Polymorphism of DNA repair gene XRCC1 and hepatitis-related hepatocellular carcinoma risk in Indian population. Mol Cell Biochem 327(1–2):7–13
Jia Z, Su H, Li X, Xu X, Yin Z (2010) Polymorphisms of UGT1A7 and XRCC1 are associated with an increased risk of hepatocellular carcinoma in Northeast China. Chin J Cancer Res 22(4):22–266 (article in Chinese)
Zeng X, Yu H, Qiu X, Ji L, Li L (2010) A case-control study of polymorphism of XRCC1 gene and the risk of hepatocellular carcinoma. Chin J Control Prev 14(8):760–763 (article in Chinese)
Tang Y, Li X, Liu T, Yang J, Luo J, Li Z (2011) Genetic polymorphisms of DNA repair genes in patients with hepatocellular carcinoma. Shandong Med J 12(11):2947–2950 (article in Chinese)
Pan HZ, Liang J, Yu Z, Lun LM, Li H, Wang Q (2011) Polymorphism of DNA repair gene XRCC1 and hepatocellular carcinoma risk in Chinese population. APJCP 12(11):2947–2950
Li QW, Lu CR, Ye M, Xiao WH, Liang J (2012) Evaluation of DNA repair gene XRCC1 polymorphism in prediction and prognosis of hepatocellular carcinoma risk. APJCP 13(1):191–194
Canalle R, da Silva SAV, Scrideli CA, de Paula Queiroz RG, Tone LG (2006) Polymorphisms in the thymidylate synthase promoter and the DNA repair genes XRCC1 and XPD in a Brazilian population. Environ Mol Mutagen 47(9):725–732
Figueiredo JC, Knight JA, Briollais L, Andrulis IL, Ozcelik H (2004) Polymorphisms XRCC1-R399Q and XRCC3-T241M and the risk of breast cancer at the Ontario site of the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev 13(4):583–591
Ladiges W, Wiley J, MacAuley A (2003) Polymorphisms in the DNA repair gene XRCC1 and age-related disease. Mech Ageing Dev 124(1):27–32
Goode EL, Ulrich CM, Potter JD (2002) Polymorphisms in DNA repair genes and associations with cancer risk. Cancer Epidemiol Biomarkers Prev 11(12):1513–1530
Hu Z, Ma H, Chen F, Wei Q, Shen H (2005) XRCC1 polymorphisms and cancer risk: a meta-analysis of 38 case-control studies. Cancer Epidemiol Biomarkers Prev 14(7):1810–1818
Chen B, Zhou Y, Yang P, Wu XT (2012) Polymorphisms of XRCC1 and gastric cancer susceptibility: a meta-analysis. Mol Biol Rep 39(2):1305–1313
Nissar S, Lone TA, Banday MZ, Rasool R, Chowdri NA, Parray FQ, Abdullah S, Sameer AS (2013) Arg399Gln polymorphism of XRCC1 gene and risk of colorectal cancer in Kashmir: a case control study. Oncol Lett 5(3):959–963
Dai L, Duan F, Wang P, Song C, Wang K, Zhang J (2012) XRCC1 gene polymorphisms and lung cancer susceptibility: a meta-analysis of 44 case-control studies. Mol Biol Rep 39(10):9535–9547
Kirkham JJ, Riley RD, Williamson PR (2012) A multivariate meta-analysis approach for reducing the impact of outcome reporting bias in systematic reviews. Stat Med 31(20):2179–2195
Acknowledgments
This study was supported by a grant from the National Natural Science Foundation of China (30872169) and the Natural Science Foundation of ShanDong Province, China (Contract No. ZR2011HM031).
Disclosures
The authors promised there were not any possible conflicts of interest in this research.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Qi, Y., Cui, L., Song, Y. et al. XRCC1 Arg399Gln genetic polymorphism and the risk of hepatocellular carcinoma: a meta-analysis. Mol Biol Rep 41, 879–887 (2014). https://doi.org/10.1007/s11033-013-2929-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-013-2929-0