Tumor Biology

, Volume 35, Issue 1, pp 759–764 | Cite as

Single-nucleotide polymorphisms of GPX1 and MnSOD and susceptibility to bladder cancer: a systematic review and meta-analysis

  • Ming Cao
  • Xin Mu
  • Chen Jiang
  • Guoliang Yang
  • Haige ChenEmail author
  • Wei Xue
Research Article


Reactive oxygen species-related damage plays a critical role in carcinogenesis. Glutathione peroxidase 1 (GPX1) and mitochondrial superoxide dismutase (MnSOD) are two key antioxidant enzymes in the defense system against reactive oxygen species. This systematic review and meta-analysis was designed to evaluate the association of single-nucleotide polymorphisms in GPX1 and MnSOD genes with susceptibility to bladder cancer risk. Online databases of PubMed, Embase, China National Knowledge Infrastructure, and SinoMed were searched to identify eligible studies. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated to estimated the association strength. The fixed effects model and random effects model were used to pool the data from different studies. By pooling all eligible studies, we found that the GPX1 Pro198Leu polymorphism was associated with a significantly increased risk of bladder cancer (Leu vs. Pro, OR = 2.111, 95 % CI = 1.020–4.368, heterogeneity (p < 0.001); LeuPro/LeuLeu vs. ProPro, OR = 1.876, 95 % CI = 1.011–3.480, heterogeneity (p < 0.001)). No significant association of MnSOD Ala-9Val polymorphism with cancer risk was observed (AlaVal/ValVal vs. AlaAla, OR = 0.966, 95 % CI = 0.754–1.239, heterogeneity (p = 0.390); Vla vs. Ala, OR = 1.038, 95 % CI = 0.782–1.377, heterogeneity (p = 0.015)). This systematic review and meta-analysis demonstrated that the GPX1 Pro198Leu polymorphism significantly increased susceptibility to bladder cancer, while the MnSOD Ala-9Val polymorphism was not associated with bladder cancer risk.


GPX1 MnSOD Polymorphism Susceptibility Bladder cancer 


Conflicts of interest


Supplementary material

13277_2013_1103_Fig5_ESM.jpg (13 kb)

Supplementary material Fig. S1 Sensitivity analysis of Leu vs. Pro of GPX1 Pro198Leu polymorphism (JPEG 13 kb)

13277_2013_1103_MOESM1_ESM.tif (145 kb)
High resolution (TIFF 145 kb)


  1. 1.
    Lamm DL, Griffith JG. Intravesical therapy: does it affect the natural history of superficial bladder cancer? Semin Urol. 1992;10(1):39–44.PubMedGoogle Scholar
  2. 2.
    Marcus PM, Hayes RB, Vineis P, Garcia-Closas M, Caporaso NE, Autrup H, et al. Cigarette smoking, N-acetyltransferase 2 acetylation status, and bladder cancer risk: a case-series meta-analysis of a gene–environment interaction. Cancer Epidemiol Biomarkers Prev. 2000;9(5):461–7.PubMedGoogle Scholar
  3. 3.
    Zeegers MP, Kellen E, Buntinx F, van den Brandt PA. The association between smoking, beverage consumption, diet and bladder cancer: a systematic literature review. World J Urol. 2004;21(6):392–401.PubMedCrossRefGoogle Scholar
  4. 4.
    St Clair DK, Jordan JA, Wan XS, Gairola CG. Protective role of manganese superoxide dismutase against cigarette smoke-induced cytotoxicity. J Toxicol Environ Health. 1994;43(2):239–49.PubMedCrossRefGoogle Scholar
  5. 5.
    Frederiks WM, Bosch KS, Hoeben KA, van Marle J, Langbein S. Renal cell carcinoma and oxidative stress: the lack of peroxisomes. Acta Histochem. 2010;112(4):364–71.PubMedCrossRefGoogle Scholar
  6. 6.
    Oberley TD, Oberley LW. Antioxidant enzyme levels in cancer. Histol Histopathol. 1997;12(2):525–35.PubMedGoogle Scholar
  7. 7.
    Wallace DC. Mitochondrial diseases in man and mouse. Science. 1999;283(5407):1482–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Arthur JR. The glutathione peroxidases. Cell Mol Life Sci. 2000;57(13–14):1825–35.PubMedGoogle Scholar
  9. 9.
    Kucukgergin C, Gokpinar M, Sanli O, Tefik T, Oktar T, Seckin S. Association between genetic variants in glutathione peroxidase 1 (GPx1) gene, GPx activity and the risk of prostate cancer. Minerva Urol Nefrol. 2011;63(3):183–90.PubMedGoogle Scholar
  10. 10.
    Kucukgergin C, Sanli O, Amasyali AS, Tefik T, Seckin S. Genetic variants of MnSOD and GPX1 and susceptibility to bladder cancer in a Turkish population. Med Oncol. 2012;29(3):1928–34.PubMedCrossRefGoogle Scholar
  11. 11.
    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(6):973–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Goerlitz D, El Daly M, Abdel-Hamid M, Saleh DA, Goldman L, El Kafrawy S, et al. GSTM1, GSTT1 null variants, and GPX1 single nucleotide polymorphism are not associated with bladder cancer risk in Egypt. Cancer Epidemiol Biomarkers Prev. 2011;20(7):1552–4.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Paz-y-Miño C, Munoz MJ, Lopez-Cortes A, Cabrera A, Palacios A, Castro B, et al. Frequency of polymorphisms pro198leu in GPX-1 gene and ile58thr in MnSOD gene in the altitude Ecuadorian population with bladder cancer. Oncol Res. 2010;18(8):395–400.PubMedCrossRefGoogle Scholar
  15. 15.
    Ichimura Y, Habuchi T, Tsuchiya N, Wang L, Oyama C, Sato K, et al. Increased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant. J Urol. 2004;172(2):728–32.PubMedCrossRefGoogle Scholar
  16. 16.
    Vineis P, Veglia F, Garte S, Malaveille C, Matullo G, Dunning A, et al. Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers. Ann Oncol. 2007;18(7):1230–42.PubMedCrossRefGoogle Scholar
  17. 17.
    Cengiz M, Ozaydin A, Ozkilic AC, Dedekarginoglu G. The investigation of GSTT1, GSTM1 and SOD polymorphism in bladder cancer patients. Int Urol Nephrol. 2007;39(4):1043–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Terry PD, Umbach DM, Taylor JA. No association between SOD2 or NQO1 genotypes and risk of bladder cancer. Cancer Epidemiol Biomarkers Prev. 2005;14(3):753–4.PubMedCrossRefGoogle Scholar
  19. 19.
    Manuguerra M, Matullo G, Veglia F, Autrup H, Dunning AM, Garte S, et al. Multi-factor dimensionality reduction applied to a large prospective investigation on gene–gene and gene–environment interactions. Carcinogenesis. 2007;28(2):414–22.PubMedCrossRefGoogle Scholar
  20. 20.
    IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Tobacco smoke and involuntary smoking. IARC Monogr Eval Carcinog Risks Hum. 2004;83:1–1438.Google Scholar
  21. 21.
    Sutton A, Imbert A, Igoudjil A, Descatoire V, Cazanave S, Pessayre D, et al. The manganese superoxide dismutase ala16val dimorphism modulates both mitochondrial import and MRNA stability. Pharmacogenet Genomics. 2005;15(5):311–9.PubMedCrossRefGoogle Scholar
  22. 22.
    McCord JM. Superoxide dismutase in aging and disease: an overview. Methods Enzymol. 2002;349:331–41.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Ming Cao
    • 1
  • Xin Mu
    • 1
  • Chen Jiang
    • 1
  • Guoliang Yang
    • 1
  • Haige Chen
    • 1
    Email author
  • Wei Xue
    • 1
  1. 1.Department of Urology, Renji Hospital, School of MedicineShanghai Jiaotong UniversityShanghaiChina

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