Tumor Biology

, Volume 34, Issue 5, pp 2551–2556

Association between NQO1 C609T polymorphism and bladder cancer susceptibility: a systemic review and meta-analysis

Research Article


There is growing evidence for the important roles of genetic factors in the host’s susceptibility to bladder cancer. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of quinoid compounds into hydroquinones. Since the NQO1 C609T polymorphism is linked to enzymatic activity of NQO1, it has also been hypothesized that NQO1 C609T polymorphism may affect the host’s susceptibility to bladder cancer by modifying the exposure to carcinogens. There were many studies carried out to assess the association between NQO1 C609T polymorphism and bladder cancer risk, but they reported contradictory results. We conducted a meta-analysis to examine the hypotheses that the NQO1 C609T polymorphism modifies the risk of bladder cancer. Eleven case–control studies with 2,937 bladder cancer cases and 3,008 controls were included in the meta-analysis. Overall, there was no obvious association between NQO1 C609T polymorphism and bladder cancer susceptibility (for T versus C: odds ratio (OR) = 1.12, 95 % confidence interval (95 %CI) 0.99–1.26, POR = 0.069; for TT versus CC: OR = 1.31, 95 %CI 0.95–1.81, POR = 0.100; for TT/CT versus CC: OR = 1.06, 95 %CI 0.95–1.18, POR = 0.304; for TT versus CT/CC: OR = 1.29, 95 %CI 0.94–1.77, POR = 0.112). After adjusting for heterogeneity, meta-analysis of those left 10 studies showed that there was an obvious association between NQO1 C609T polymorphism and bladder cancer susceptibility (for T versus C: OR = 1.18, 95 %CI 1.06–1.31, POR = 0.003; for TT versus CC: OR = 1.47, 95 %CI 1.14–1.90, POR = 0.003; for TT/CT versus CC: OR = 1.16, 95 %CI 1.01–1.34, POR = 0.036; for TT versus CT/CC: OR = 1.39, 95 %CI 1.10–1.75, POR = 0.006). There was low risk of publication bias. Therefore, our meta-analysis suggests that NQO1 C609T polymorphism is associated with bladder cancer susceptibility.


NQO1 Polymorphism Bladder cancer Meta-analysis 


  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.
    Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet. 2009;374:239–49.CrossRefPubMedGoogle Scholar
  3. 3.
    Mitra AP, Cote RJ. Molecular pathogenesis and diagnostics of bladder cancer. Annu Rev Pathol. 2009;4:251–85.CrossRefPubMedGoogle Scholar
  4. 4.
    Wu X, Hildebrandt MA, Chang DW. Genome-wide association studies of bladder cancer risk: a field synopsis of progress and potential applications. Cancer Metastasis Rev. 2009;28:269–80.CrossRefPubMedGoogle Scholar
  5. 5.
    Golka K, Selinski S, Lehmann ML, Blaszkewicz M, Marchan R, Ickstadt K, et al. Genetic variants in urinary bladder cancer: collective power of the “wimp SNPs”. Arch Toxicol. 2011;85:539–54.CrossRefPubMedGoogle Scholar
  6. 6.
    Vasiliou V, Ross D, Nebert DW. Update of the NAD(P)H:quinone oxidoreductase (NQO) gene family. Hum Genomics. 2006;2:329–35.PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Ross D, Siegel D. NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase), functions and pharmacogenetics. Methods Enzymol. 2004;382:115–44.CrossRefPubMedGoogle Scholar
  8. 8.
    Guha N, Chang JS, Chokkalingam AP, Wiemels JL, Smith MT, Buffler PA. NQO1 polymorphisms and de novo childhood leukemia: a huge review and meta-analysis. Am J Epidemiol. 2008;168:1221–32.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Siegel D, Yan C, Ross D. NAD(P)H:quinone oxidoreductase 1 (NQO1) in the sensitivity and resistance to antitumor quinones. Biochem Pharmacol. 2012;83:1033–40.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Misra V, Grondin A, Klamut HJ, Rauth AM. Assessment of the relationship between genotypic status of a DT-diaphorase point mutation and enzymatic activity. Br J Cancer. 2000;83:998–1002.PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Siegel D, McGuinness SM, Winski SL, Ross D. Genotype-phenotype relationships in studies of a polymorphism in NAD(P)H:quinone oxidoreductase 1. Pharmacogenetics. 1999;9:113–21.CrossRefPubMedGoogle Scholar
  12. 12.
    Wang YH, Lee YH, Tseng PT, Shen CH, Chiou HY. Human NAD(P)H:quinone oxidoreductase 1 (NQO1) and sulfotransferase 1A1 (SULT1A1) polymorphisms and urothelial cancer risk in Taiwan. J Cancer Res Clin Oncol. 2008;134:203–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Terry PD, Umbach DM, Taylor JA. No association between SOD2 or NQO1 genotypes and risk of bladder cancer. Cancer Epidemiol Biomark Prev. 2005;14:753–4.CrossRefGoogle Scholar
  14. 14.
    Schulz WA, Krummeck A, Rosinger I, Eickelmann P, Neuhaus C, Ebert T, et al. Increased frequency of a null-allele for NAD(P)H: quinone oxidoreductase in patients with urological malignancies. Pharmacogenetics. 1997;7:235–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Sanyal S, Festa F, Sakano S, Zhang Z, Steineck G, Norming U, et al. Polymorphisms in DNA repair and metabolic genes in bladder cancer. Carcinogenesis. 2004;25:729–34.CrossRefPubMedGoogle Scholar
  16. 16.
    Park SJ, Zhao H, Spitz MR, Grossman HB, Wu X. An association between NQO1 genetic polymorphism and risk of bladder cancer. Mutat Res. 2003;536:131–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Moore LE, Wiencke JK, Bates MN, Zheng S, Rey OA, Smith AH. Investigation of genetic polymorphisms and smoking in a bladder cancer case–control study in Argentina. Cancer Lett. 2004;211:199–207.CrossRefPubMedGoogle Scholar
  18. 18.
    Hung RJ, Boffetta P, Brennan P, Malaveille C, Gelatti U, Placidi D, et al. Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk. Carcinogenesis. 2004;25:973–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Fu J, Chen BC. Relationship between genetic polymorphism of NQO1 and susceptibility to bladder cancer. J Chin Oncol. 2012;18:561–4.Google Scholar
  20. 20.
    Figueroa JD, Malats N, Garcia-Closas M, Real FX, Silverman D, Kogevinas M, et al. Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes. Carcinogenesis. 2008;29:1955–62.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Choi JY, Lee KM, Cho SH, Kim SW, Choi HY, Lee SY, et al. CYP2E1 and NQO1 genotypes, smoking and bladder cancer. Pharmacogenetics. 2003;13:349–55.CrossRefPubMedGoogle Scholar
  22. 22.
    Broberg K, Bjork J, Paulsson K, Hoglund M, Albin M. Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer. Carcinogenesis. 2005;26:1263–71.CrossRefPubMedGoogle Scholar
  23. 23.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    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
  25. 25.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.CrossRefPubMedGoogle Scholar
  26. 26.
    Galbraith R. A note on graphical presentation of estimated odds ratios from several clinical trials. Stat Med. 1988;7:889–94.CrossRefPubMedGoogle Scholar
  27. 27.
    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
  28. 28.
    Kiltie AE. Common predisposition alleles for moderately common cancers: bladder cancer. Curr Opin Genet Dev. 2010;20:218–24.CrossRefPubMedGoogle Scholar
  29. 29.
    Han SS, Rosenberg PS, Garcia-Closas M, Figueroa JD, Silverman D, Chanock SJ, et al. Likelihood ratio test for detecting gene (G)-environment (E) interactions under an additive risk model exploiting G-E independence for case–control data. Am J Epidemiol. 2012;176:1060–7.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Boffetta P, Winn DM, Ioannidis JP, Thomas DC, Little J, Smith GD, et al. Recommendations and proposed guidelines for assessing the cumulative evidence on joint effects of genes and environments on cancer occurrence in humans. Int J Epidemiol. 2012;41:686–704.PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Panagiotakis GI, Papadogianni D, Chatziioannou MN, Lasithiotaki I, Delakas D, Spandidos DA. Association of human herpes, papilloma and polyoma virus families with bladder cancer. Tumour Biol. 2013;34:71–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Zhang Y, Wang X, Zhang W, Gong S. An association between XPC Lys939Gln polymorphism and the risk of bladder cancer: a meta-analysis. Tumour Biol. 2013;34:973–82.CrossRefPubMedGoogle Scholar
  33. 33.
    Fan R, Zhong M, Wang S, Zhang Y, Andrew A, Karagas M, et al. Entropy-based information gain approaches to detect and to characterize gene-gene and gene-environment interactions/correlations of complex diseases. Genet Epidemiol. 2011;35:706–21.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  1. 1.Department of Urology, Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghaiChina
  2. 2.Department of Urology, Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Personalised recommendations