Skip to main content
SpringerLink
Log in

Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk

International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Glutathione peroxidase 1 (GPX1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides. Some epidemiological studies have correlated low GPX activity or particular GPX1 polymorphisms with enhanced risk of cancer, although these correlations have not been consistently observed in all populations. Therefore, we conducted the present study to evaluate the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Macedonian population. The GPX1 Pro198Leu genotype was determined in 82 prostate cancer cases and 123 control individuals. We found an overall protective effect of the variant Leu allele of the GPX1 polymorphism on the prostate cancer risk. Heterozygous carriers of the variant Leu allele had a significantly lower risk of prostate cancer compared with homozygous wild-type individuals (OR, 0.38; 95% CI, 0.20–0.75; P = 0.004). Erythrocyte GPX activity was analyzed in 73 cases and 91 controls. The erythrocyte GPX activity in the cancer group was lower than in the healthy controls. Additionally, we compared the erythrocyte GPX activity in the control group of 90 subjects and found no significant differences by genotype. These findings suggest that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism and that the combination of genetic factors involved in oxidative response with environmental carcinogens may play an important role in prostate carcinogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66

    Article  PubMed  Google Scholar 

  2. Walsh PC, DeWeese TL, Eisenberger MA (2007) Localized Prostate Cancer. N Engl J Med 357:2696–2705

    Article  PubMed  CAS  Google Scholar 

  3. Forsberg L, de Faire U, Morgenstern R (2001) Oxidative stress, human genetic variation, and disease. Arch Biochem Biophys 389:84–93

    Article  PubMed  CAS  Google Scholar 

  4. Cooke M, Evans M, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J 17:1195–1214

    Article  PubMed  CAS  Google Scholar 

  5. Ray G, Batra S, Shukla NK, Deo S, Raina V, Ashok S et al (2000) Lipid peroxidation, free radical production and antioxidant status in breast cancer. Breast Cancer Res Treat 59:163–170

    Article  PubMed  CAS  Google Scholar 

  6. Aydin A, Arsova-Sarafinovska Z, Sayal A, Eken A, Erdem O, Erten K, Ozgok Y, Dimovski A (2006) Oxidative stress and antioxidant status in non-metastatic prostate cancer and benign prostatic hyperplasia. Clin Biochem 39:176–179

    Article  PubMed  CAS  Google Scholar 

  7. Dursun H, Bilici M, Uyanik A, Okcu N (2006) Akyuz M: Antioxidant enzyme activities and lipid peroxidation levels in erythrocytes of patients with oesophageal and gastric cancer. J Int Med Res 34:193–199

    PubMed  CAS  Google Scholar 

  8. Saygili EI, Akcay T, Konukoglu D, Papilla C (2003) Glutathione and glutathione-related enzymes in colorectal cancer patients. J Toxicol Environ Health A 66:411–415

    Article  PubMed  CAS  Google Scholar 

  9. Ravn-Haren G, Olsen A, Tjonneland A, Dragsted LO, Nexo BA, Wallin H et al (2006) Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study. Carcinogenesis 27:820–825

    Article  PubMed  CAS  Google Scholar 

  10. Arthur JR (2000) The glutathione peroxidases. Cell Moll Life Sci 57:1825–1835

    Article  CAS  Google Scholar 

  11. Chu FF, Doroshow JH, Esworthy RS (1993) Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI. J Biol Chem 268:2571–2576

    PubMed  CAS  Google Scholar 

  12. Takahashi K, Akasaka M, Yamamoto Y, Kobayashi C, Mizoguchi J, Koyama J (1990) Primary structure of human plasma glutathione peroxidase deduced from cDNA sequences. J Biochem 108:145–148

    PubMed  CAS  Google Scholar 

  13. Maiorino M, Chu FF, Ursini F, Davies KJ, Doroshow JH, Esworthy RS (1991) Phospholipid hydroperoxide glutathione peroxidase is the 18-kDa selenoproteins expressed in human tumor cell lines. J Biol Chem 266:7728–32

    PubMed  CAS  Google Scholar 

  14. de Haan JB, Bladier C, Griffiths P, Kelner M, O’Shea RD, Cheung NS et al (1998) Mice with a homozygous null mutation for the most abundant glutathione peroxidase, GPX1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide. J Biol Chem 273:22528–22536

    Article  PubMed  Google Scholar 

  15. Moscow JA, Schmidt L, Ingram DT, Gnarra J, Johnson B, Cowan KH (1994) Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer. Carcinogenesis 15:2769–2773

    Article  PubMed  CAS  Google Scholar 

  16. Kote-Jarai Z, Durocher F, Edwards SM, Hamoudi R, Jackson RA, Ardern-Jones A et al (2002) Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer. Prostate Cancer Prostatic Dis 5:189–192

    Article  PubMed  CAS  Google Scholar 

  17. Hu YJ, Diamond AM (2003) Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Res 63:3347–3351

    PubMed  CAS  Google Scholar 

  18. Knight JA, Onay UV, Wells S, Li H, Shi EJ, Andrulis JL (2004) Genetic variants of GPX1 and SOD2 and breast cancer risk at the Ontario site of breast cancer family registry. Cancer Epidemiol Biomark Prev 13:146–149

    Article  CAS  Google Scholar 

  19. Cox DG, Hankinson SE, Kraft P, Hunter DJ (2004) No association between GPX1Pro198Leu and breast cancer risk. Cancer Epidemiol Biomark Prev 13:1821–1822

    CAS  Google Scholar 

  20. Vogel U, Olsen A, Wallin H, Overvad K, Tjonneland A, Nexo BA (2004) No association between GPX Pro198Leu and risk of basal cell carcinoma. Cancer Epidemiol Biomarkers Prev 13:1412–1413

    PubMed  CAS  Google Scholar 

  21. Hansen R, Saebo M, Skjelbred CF, Nexo BA, Hagen PC, Bock G et al (2005) GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of colorectal adenomas and colorectal cancer. Cancer Lett 229:85–91

    Article  PubMed  CAS  Google Scholar 

  22. Yang P, Bamlet WR, Ebbert JO, Taylor WR, de Andrade M (2004) Glutathione pathway genes and lung cancer risk in young and old populations. Carcinogenesis 25:1935–1944

    Article  PubMed  CAS  Google Scholar 

  23. Raaschou-Nielsen O, Sorensen O, Hansen RD, Frederiksen K, Anne Tjonneland A, Overvad K (2007) GPX1 Pro198Leu polymorphism, interactions with smoking and alcohol consumption, and risk for lung cancer. Cancer Lett 247:293–300

    Article  PubMed  CAS  Google Scholar 

  24. Forsberg L, de Faire U, Marklund SL, Andersson PM, Stegmayr B, Morgenstern R (2000) Phenotype determination of a common Pro-Leu polymorphism in human glutathione peroxidase 1. Blood Cells Mol Dis 26:423–426

    Article  PubMed  CAS  Google Scholar 

  25. Bostwick DG (1994) Grading prostate cancer. Am J Clin Pathol 102:S38–S56

    PubMed  CAS  Google Scholar 

  26. Poncz M, Solowiejczyk D, Harpel B, Mory Y, Schwartz E, Surrey S (1982) Construction of human gene libraries from small amounts of peripheral blood: analysis of beta-like globin genes. Hemoglobin 6:27–36

    Article  PubMed  CAS  Google Scholar 

  27. Ratnasinghe D, Tangrea JA, Andersen MR, Barrett MJ, Virtamo J, Taylor PR, Albanes D (2000) Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk. Cancer Res 60:6381–6383

    PubMed  CAS  Google Scholar 

  28. Aydin A, Hilmi O, Sayal A, Ozata M, Sahin G, Isimer A (2001) Oxidative stress and nitric oxide related parameters in type II diabetes mellitus: effects of glycemic control. Clin Biochem 34:65–70

    Article  PubMed  CAS  Google Scholar 

  29. Choi JY, Neuhouser ML, Barnett M, Hudson M, Kristal AR, Thornquist M (2007) Polymorphisms in oxidative stress-related genes are not associated with prostate cancer risk in heavy smokers. Cancer Epidemiol Biomarkers Prev 16:1115–1120

    Article  PubMed  CAS  Google Scholar 

  30. Jung K, Seidel B, Rudolph B, Lein M, Cronauer MV, Henke W et al (1997) Antioxidant enzymes in malignant prostate cell lines and in primary cultured prostatic cells. Free Radic Biol Med 23:127–133

    Article  PubMed  CAS  Google Scholar 

  31. Baker AM, Oberley LW, Cohen MB (1997) Expression of antioxidant enzymes in human prostatic adenocarcinoma. Prostate 32:229–233

    Article  PubMed  CAS  Google Scholar 

  32. Gate L, Paul J, Nguyen Ba G, Tew KD, Tapiero H (1990) Oxidative stress induced in pathologies: the role of antioxidants. Biomed Pharmacother 53:169–180

    Article  Google Scholar 

  33. Aznar S, Lacal JC (2001) Rho signals to cell growth and apoptosis. Cancer Lett 165:1–10

    Article  PubMed  CAS  Google Scholar 

  34. Dragsted LO, Pedersen A, Hermetter A, Basu S, Hansen M, Haren GR et al (2004) The 6-a-day study: effects of fruit and vegetables on markers of oxidative stress and antioxidative defense in healthy nonsmokers. Am J Clin Nutr 79:1060–1072

    PubMed  CAS  Google Scholar 

  35. Neve J (1995) Human selenium supplementation as assessed by changes in blood selenium concentration and glutathione peroxidase activity. J Trace Elem Med Biol 9:65–73

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This research work was supported by a grant from the Turkish Scientific and Technical Research Association, TUBITAK (to AA) and grants from the Ministry of Education and Science of the Republic of Macedonia (to AJD and AS).

Author information

Authors and Affiliations

  1. Department of Drug Quality Control, Republic Institute for Health Protection, Skopje, Republic of Macedonia

    Zorica Arsova-Sarafinovska

  2. Department of Molecular Biology and Genetics, Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, Vodnjanska 17, Skopje, Republic of Macedonia

    Nadica Matevska & Aleksandar J. Dimovski

  3. Department of Toxicology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey

    Ayse Eken, Onur Erdem, Ahmet Sayal & Ahmet Aydin

  4. University Clinic of Urology, Skopje, Republic of Macedonia

    Daniel Petrovski & Vladimir Georgiev

  5. Faculty of Medicine, Institute of Pathology, Skopje, Republic of Macedonia

    Saso Banev

  6. University Clinic of Nephrology, Skopje, Republic of Macedonia

    Sonja Dzikova & Aleksandar Sikole

Authors
  1. Zorica Arsova-Sarafinovska
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nadica Matevska
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ayse Eken
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniel Petrovski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Saso Banev
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sonja Dzikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vladimir Georgiev
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Aleksandar Sikole
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Onur Erdem
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ahmet Sayal
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ahmet Aydin
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Aleksandar J. Dimovski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aleksandar J. Dimovski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arsova-Sarafinovska, Z., Matevska, N., Eken, A. et al. Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk. Int Urol Nephrol 41, 63–70 (2009). https://doi.org/10.1007/s11255-008-9407-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-008-9407-y

Keywords

search

Navigation