Tumor Biology

, Volume 35, Issue 1, pp 269–275 | Cite as

The rs1050450 C > T polymorphism of GPX1 is associated with the risk of bladder but not prostate cancer: evidence from a meta-analysis

  • Tongyi Men
  • Xiaoming Zhang
  • Jiwei Yang
  • Bin Shen
  • Xianduo Li
  • Dongdong Chen
  • Jianning Wang
Research Article


Glutathione peroxidase (GPX) is an endogenous antioxidant enzyme counteracting oxidative stress. Accumulating evidence has demonstrated that the GPX1 rs1050450 C > T polymorphism may modulate cancer risk, but the association of GPX1 rs1050450 polymorphism with bladder cancer (BC) and prostate cancer (PCa) is still inconclusive. This meta-analysis was designed to determine the exact association of GPX1 rs1050450 C > T polymorphism with the risk of bladder cancer and prostate cancer. Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated to estimate the association strength. Databases of PubMed, EMBASE, and China National Knowledge Infrastructure were searched to retrieve eligible studies. In total, ten eligible studies with 6,194 participants were included. By pooling all eligible studies, we found that carriers of the variant T allele were associated with a significantly increased risk of urinary tract cancer (T vs. C: OR = 1.459 and 95 % CI, 1.086–1.962; CT/TT vs. CC: OR = 1.411 and 95 % CI, 1.053–1.891). In stratified analysis, we observed that the rs1050450 C > T polymorphism was significantly associated with an increased risk of BC (T vs. C: OR = 2.111 and 95 % CI, 1.020–4.368; CT/TT vs. CC: OR = 1.876 and 95 % CI, 1.011–3.480), while the association was not significant for PCa. Egger’s test and Begg’s test revealed no publication bias. The present meta-analysis provides evidence that the GPX1 rs1050450 C > T polymorphism leads to an increased risk of BC but not the risk of PCa.


GPX1 Prostate cancer Bladder cancer Meta-analysis 


Conflicts of interest



  1. 1.
    Walsh PC, DeWeese TL, Eisenberger MA. Clinical practice. Localized prostate cancer. N Engl J Med. 2007;357(26):2696–705.PubMedCrossRefGoogle Scholar
  2. 2.
    MacVicar AD. Bladder cancer staging. BJU Int. 2000;86 Suppl 1:111–22.PubMedGoogle Scholar
  3. 3.
    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
  4. 4.
    Pryor WA. Cigarette smoke radicals and the role of free radicals in chemical carcinogenicity. Environ Health Perspect. 1997;105 Suppl 4:875–82.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Brown NS, Bicknell R. Hypoxia and oxidative stress in breast cancer. Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Res. 2001;3(5):323–7.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Arthur JR. The glutathione peroxidases. Cell Mol Life Sci. 2000;57(13–14):1825–35.PubMedGoogle Scholar
  7. 7.
    Bhabak KP, Mugesh G. Functional mimics of glutathione peroxidase: bioinspired synthetic antioxidants. Acc Chem Res. 2010;43(11):1408–19.PubMedCrossRefGoogle Scholar
  8. 8.
    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
  9. 9.
    Hansen R, Saebo M, Skjelbred CF, Nexo BA, Hagen PC, Bock G, et al. Gpx Pro198leu and Ogg1 Ser326cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer. Cancer Lett. 2005;229(1):85–91.PubMedCrossRefGoogle Scholar
  10. 10.
    Meplan C, Hughes DJ, Pardini B, Naccarati A, Soucek P, Vodickova L, et al. Genetic variants in selenoprotein genes increase risk of colorectal cancer. Carcinogenesis. 2010;31(6):1074–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Yang P, Bamlet WR, Ebbert JO, Taylor WR, de Andrade M. Glutathione pathway genes and lung cancer risk in young and old populations. Carcinogenesis. 2004;25(10):1935–44.PubMedCrossRefGoogle Scholar
  12. 12.
    Rosenberger A, Illig T, Korb K, Klopp N, Zietemann V, Wolke G, et al. Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years. BMC Cancer. 2008;8:60.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Hu YJ, Dolan ME, Bae R, Yee H, Roy M, Glickman R, et al. Allelic loss at the Gpx-1 locus in cancer of the head and neck. Biol Trace Elem Res. 2004;101(2):97–106.PubMedCrossRefGoogle Scholar
  14. 14.
    Cebrian A, Pharoah PD, Ahmed S, Smith PL, Luccarini C, Luben R, et al. Tagging single-nucleotide polymorphisms in antioxidant defense enzymes and susceptibility to breast cancer. Cancer Res. 2006;66(2):1225–33.PubMedCrossRefGoogle Scholar
  15. 15.
    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
  16. 16.
    Paz-y-Mino 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 lltitude Ecuadorian population with badder cancer. Oncol Res. 2010;18(8):395–400.PubMedCrossRefGoogle Scholar
  17. 17.
    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
  18. 18.
    Karunasinghe N, Han DY, Goudie M, Zhu S, Bishop K, Wang A, et al. Prostate disease risk factors among a New Zealand cohort. J Nutrigenet Nutrigenomics. 2012;5(6):339–51.PubMedCrossRefGoogle Scholar
  19. 19.
    Arsova-Sarafinovska Z, Matevska N, Eken A, Petrovski D, Banev S, Dzikova S, et al. Glutathione peroxidase 1 (Gpx1) genetic polymorphism, erythrocyte Gpx activity, and prostate cancer risk. Int Urol Nephrol. 2009;41(1):63–70.PubMedCrossRefGoogle Scholar
  20. 20.
    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
  21. 21.
    Choi JY, Neuhouser ML, Barnett M, Hudson M, Kristal AR, Thornquist M, et al. Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers. Cancer Epidemiol Biomarkers Prev. 2007;16(6):1115–20.PubMedCrossRefGoogle Scholar
  22. 22.
    Lau J, Ioannidis JP, Schmid CH. Quantitative synthesis in systematic reviews. Ann Intern Med. 1997;127(9):820–6.PubMedCrossRefGoogle 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(7109):629–34.PubMedCrossRefGoogle Scholar
  24. 24.
    Geybels MS, Hutter CM, Kwon EM, Ostrander EA, Fu R, Feng Z, et al. Variation in selenoenzyme genes and prostate cancer risk and survival. Prostate. 2013;73(7):734–42.PubMedCrossRefGoogle Scholar
  25. 25.
    Kote-Jarai Z, Durocher F, Edwards SM, Hamoudi R, Jackson RA, Ardern-Jones A, et al. Association between the Gcg polymorphism of the selenium dependent Gpx1 gene and the risk of young onset prostate cancer. Prostate Cancer Prostatic Dis. 2002;5(3):189–92.PubMedCrossRefGoogle Scholar
  26. 26.
    Abe M, Xie W, Regan MM, King IB, Stampfer MJ, Kantoff PW, et al. Single-nucleotide polymorphisms within the antioxidant defence system and associations with aggressive prostate cancer. BJU Int. 2011;107(1):126–34.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Cheng TY, Barnett MJ, Kristal AR, Ambrosone CB, King IB, Thornquist MD, et al. Genetic variation in myeloperoxidase modifies the association of serum alpha-tocopherol with aggressive prostate cancer among current smokers. J Nutr. 2011;141(9):1731–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Erdem O, Eken A, Akay C, Arsova-Sarafinovska Z, Matevska N, Suturkova L, et al. Association of Gpx1 polymorphism, Gpx activity and prostate cancer risk. Hum Exp Toxicol. 2012;31(1):24–31.PubMedCrossRefGoogle Scholar
  29. 29.
    Steinbrecher A, Meplan C, Hesketh J, Schomburg L, Endermann T, Jansen E, et al. Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men. Cancer Epidemiol Biomarkers Prev. 2010;19(11):2958–68.PubMedCrossRefGoogle Scholar
  30. 30.
    Hu YJ, Diamond AM. Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Res. 2003;63(12):3347–51.PubMedGoogle Scholar
  31. 31.
    Liwei L, Chunyu L, Jie L, Ruifa H. Association between fibroblast growth factor receptor-4 gene polymorphism and risk of prostate cancer: a meta-analysis. Urol Int. 2011;87(2):159–64.PubMedCrossRefGoogle Scholar
  32. 32.
    Sterne JA, Egger M. Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis. J Clin Epidemiol. 2001;54(10):1046–55.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Tongyi Men
    • 1
  • Xiaoming Zhang
    • 1
  • Jiwei Yang
    • 1
  • Bin Shen
    • 1
  • Xianduo Li
    • 1
  • Dongdong Chen
    • 1
  • Jianning Wang
    • 1
  1. 1.Department of UrologyQianfoshan Hospital Affiliated to Shandong UniversityJinanChina

Personalised recommendations