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The NQO1 C609T polymorphism and hepatocellular carcinoma risk

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Tumor Biology

Abstract

NAD(P)H quinine oxidoreductase 1 (NQO1) enzyme plays a crucial role in the protection against oxidative stress. The polymorphism of NQO1 C609T has been implicated in the development of hepatocellular carcinoma (HCC). However, the findings were inconsistent due to different ethnicity, sample size, and source of controls in individual studies. To better estimate the association of NQO1 C609T polymorphism with HCC risk, we performed a meta-analysis of all currently available studies on the susceptibility to HCC. The meta-analysis included three independent studies with a total of 1, 595 subjects. The association was assessed under five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of HCC (ORT vs. C = 1.47, 95 % CI 1.07–2.00, P OR = 0.016; ORTT vs. CC = 2.06, 95 % CI 1.06–3.98, P OR = 0.032; ORTC vs. CC = 1.33, 95 % CI 1.06–1.67, P OR = 0.012; ORTT + TC vs. CC = 1.46, 95 % CI 1.19–1.81, P OR < 0.001; ORTT vs. CC + TC = 1.62, 95 % CI 1.25–2.09, P OR < 0.001). Stratified analyses in Asians and hospital-based case–control studies further demonstrated the significant correlation. Sensitivity analysis confirmed the reliability of these findings. Our study firstly shows that individuals carrying the NQO1 C609T variant allele and genotypes are more susceptible to HCC, particularly for Asians.

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References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  2. de Lope CR, Tremosini S, Forner A, Reig M, Bruix J. Management of HCC. J Hepatol. 2012;56 Suppl 1:S75–87.

    Article  PubMed  Google Scholar 

  3. Beasley RP. Rocks along the road to the control of HBV and HCC. Ann Epidemiol. 2009;19:231–4.

    Article  PubMed  Google Scholar 

  4. Kim DY, Han KH. Epidemiology and surveillance of hepatocellular carcinoma. Liver Cancer. 2012;1:2–14.

    Article  PubMed Central  Google Scholar 

  5. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–73. e1261.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Xu Y, Li L, Xiang X, et al. Three common functional polymorphisms in microRNA encoding genes in the susceptibility to hepatocellular carcinoma: a systematic review and meta-analysis. Gene. 2013;527:584–93.

    Article  CAS  PubMed  Google Scholar 

  7. Nahon P, Zucman-Rossi J. Single nucleotide polymorphisms and risk of hepatocellular carcinoma in cirrhosis. J Hepatol. 2012;57:663–74.

    Article  CAS  PubMed  Google Scholar 

  8. Lv L, Wang P, Zhou X, Sun B. Association between the p53 codon 72 Arg/Pro polymorphism and hepatocellular carcinoma risk. Tumour Biol. 2013;34:1451–9.

    Article  CAS  PubMed  Google Scholar 

  9. Han Y, Pu R, Han X, et al. Association of a potential functional pre-miR-218 polymorphism and its interaction with hepatitis B virus mutations with hepatocellular carcinoma risk. Liver Int. 2013. doi:10.1111/liv.12313.

    Google Scholar 

  10. Park MS, Kim SK, Shin HP, Lee SM, Chung JH. TXNDC5 gene polymorphism contributes to increased risk of hepatocellular carcinoma in the Korean male population. Anticancer Res. 2013;33:3983–7.

    CAS  PubMed  Google Scholar 

  11. Liu F, Luo L, Wei Y, et al. A functional NQO1 609C > T polymorphism and risk of hepatocellular carcinoma in a Chinese population. Tumour Biol. 2013;34:47–53.

    Article  PubMed  Google Scholar 

  12. Akkiz H, Bayram S, Bekar A, et al. No association of NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism and risk of hepatocellular carcinoma development in Turkish subjects. Asian Pac J Cancer Prev. 2010;11:1051–8.

    PubMed  Google Scholar 

  13. Wang WW, Chou XQ, Tan SK, Ren Y, Bei CH, Liu S. Association of NQO1 C609T gene polymorphism with susceptibility of hepatocellular carcinoma. Chin Gen Pract. 2012;15:1369–71 [Article in Chinese].

    Google Scholar 

  14. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.

    Article  CAS  PubMed  Google Scholar 

  15. Minelli C, Thompson JR, Abrams KR, Thakkinstian A, Attia J. The quality of meta-analyses of genetic association studies: a review with recommendations. Am J Epidemiol. 2009;170:1333–43.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Cochran WG. The comparison of percentages in matched samples. Biometrika. 1950;37:256–66.

    Article  CAS  PubMed  Google Scholar 

  17. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed Central  PubMed  Google Scholar 

  18. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.

    Article  CAS  PubMed  Google Scholar 

  19. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–48.

    CAS  PubMed  Google Scholar 

  20. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. 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 470–461.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Villanueva A, Newell P, Chiang DY, Friedman SL, Llovet JM. Genomics and signaling pathways in hepatocellular carcinoma. Semin Liver Dis. 2007;27:55–76.

    Article  CAS  PubMed  Google Scholar 

  23. Rosvold EA, McGlynn KA, Lustbader ED, Buetow KH. Identification of an NAD(P)H: quinone oxidoreductase polymorphism and its association with lung cancer and smoking. Pharmacogenetics. 1995;5:199–206.

    Article  CAS  PubMed  Google Scholar 

  24. Ross D, Kepa JK, Winski SL, Beall HD, Anwar A, Siegel D. NAD(P)H: quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chem Biol Interact. 2000;129:77–97.

    Article  CAS  PubMed  Google Scholar 

  25. Joseph P, Xie T, Xu Y, Jaiswal AK. NAD(P)H: quinone oxidoreductase1 (DT-diaphorase): expression, regulation, and role in cancer. Oncol Res. 1994;6:525–32.

    CAS  PubMed  Google Scholar 

  26. Belinsky M, Jaiswal AK. NAD(P)H: quinone oxidoreductase1 (DT-diaphorase) expression in normal and tumor tissues. Cancer Metastasis Rev. 1993;12:103–17.

    Article  CAS  PubMed  Google Scholar 

  27. Yanling H, Yuhong Z, Wenwu H, Lei X, Mingwu C. NQO1 C609T polymorphism and esophageal cancer risk: a HuGE review and meta-analysis. BMC Med Genet. 2013;14:31.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Wang Z, Hu J, Zhong J. Meta-analysis of the NAD(P)H: quinine oxidoreductase 1 gene 609 C > T polymorphism with esophageal cancer risk. DNA Cell Biol. 2012;31:560–7.

    Article  PubMed  Google Scholar 

  29. Gong M, Yi Q, Wang W. Association between NQO1 C609T polymorphism and bladder cancer susceptibility: a systemic review and meta-analysis. Tumour Biol. 2013;34:2551–6.

    Article  CAS  PubMed  Google Scholar 

  30. Guo S, Gao M, Li X, et al. Lack of association between NADPH quinone oxidoreductase 1 (NQO1) gene C609T polymorphism and lung cancer: a case–control study and a meta-analysis. PLoS One. 2012;7:e47939.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Yang FY, Guan QK, Cui YH, Zhao ZQ, Rao W, Xi Z. NAD(P)H quinone oxidoreductase 1 (NQO1) genetic C609T polymorphism is associated with the risk of digestive tract cancer: a meta-analysis based on 21 case–control studies. Eur J Cancer Prev. 2012;21:432–41.

    Article  CAS  PubMed  Google Scholar 

  32. Wu J, Zhang W, Xu A, et al. Association of epidermal growth factor and epidermal growth factor receptor polymorphisms with the risk of hepatitis B virus-related hepatocellular carcinoma in the population of North China. Genet Test Mol Biomarkers. 2013;17:595–600.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Palliyaguru DL, Wu F. Global geographical overlap of aflatoxin and hepatitis C: controlling risk factors for liver cancer worldwide. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2013;30:534–40.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Schutte K, Bornschein J, Malfertheiner P. Hepatocellular carcinoma–epidemiological trends and risk factors. Dig Dis. 2009;27:80–92.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Henan Science and Technology University, Luoyang, 471000, Henan Province, China

    Yonggang Fan, Dingwen Hu, Bing Feng & Wei Wang

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  1. Yonggang Fan
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  2. Dingwen Hu
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Correspondence to Yonggang Fan.

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Yonggang Fan and Dingwen Hu contributed equally to this work.

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Fan, Y., Hu, D., Feng, B. et al. The NQO1 C609T polymorphism and hepatocellular carcinoma risk. Tumor Biol. 35, 7343–7350 (2014). https://doi.org/10.1007/s13277-014-1712-8

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