Skip to main content

Advertisement

SpringerLink
Log in

Association of myeloperoxidase polymorphism (G463A) with cervix cancer

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Cervical cancer is the fourth most common cancer affecting women worldwide, according to the latest IARC release with 528 000 new cases every year. Infection by high-risk human papillomavirus (HPV) is necessary but not sufficient for progression to cancer. Epithelial tissues, the target of HPV infection, are heavily exposed to reactive oxygen species (ROS). Hypochlorous acid (HOCl) is a very potent ROS, and it is produced by myeloperoxidase (MPO). MPO, a lysosomal enzyme expressed in polymorphonuclear neutrophils (PMN), has the potential to kill HPV transformed cells, as a component of an intercellular induced-apoptosis pathway. This enzyme catalyzes the production of HOCl in the presence of hydrogen peroxide (H2O2). The H2O2 produced by the Doderlein’s bacillus will interact with MPO, contributing to the intercellular induced-apoptosis pathway. We studied a functional polymorphism in the promoter region of MPO (G463A) and how it may affect the risk of developing cervix cancer. A sample of 100 patients with invasive cervical cancer and 122 control women were genotyped for MPO polymorphism by PCR–RFLP method. The statistical method used was χ2. We found that women with the GG genotype had lower risk for cervical cancer than the women who displayed the heterozygous genotype GA (OR = 0.546, 95 % CI = 0.315–0.939, p = 0.028, OR = 2.210, 95 % CI = 1.257–3.886, p = 0.008, respectively). The genotype that leads to a higher concentration of ROS (GG) presents itself as a protection factor in comparison to the homozygous genotype (AA). This can be explained by the interaction of HOCl and superoxide of transformed cells that will generate apoptosis-inducing hydroxyl radicals.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin D, Forman D and Bray F (2013) Cancer Incidence and Mortality Worldwide: IARC Cancerbase. GLOBOCAN 2012 v1.0, 11 edn. IARC, IARC

  2. Castellsague X (2008) Natural history and epidemiology of HPV infection and cervical cancer. Gynecol Oncol 110:S4–S7. doi:10.1016/j.ygyno.2008.07.045

    Article  PubMed  Google Scholar 

  3. Moody CA, Laimins LA (2010) Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 10:550–560. doi:10.1038/nrc2886

    Article  CAS  PubMed  Google Scholar 

  4. Munoz N, Castellsague X, de Gonzalez AB, Gissmann L (2006) HPV in the etiology of human cancer. Vaccine 24(3):S1–S10. doi:10.1016/j.vaccine.2006.05.115

    Article  Google Scholar 

  5. Miller RA, Britigan BE (1997) Role of oxidants in microbial pathophysiology. Clin Microbiol Rev 10:1–18

    PubMed Central  CAS  PubMed  Google Scholar 

  6. Sosa V, Moline T, Somoza R, Paciucci R, Kondoh H, ME LL (2013) Oxidative stress and cancer: an overview. Ageing Res Rev 12:376–390. doi:10.1016/j.arr.2012.10.004

    Article  CAS  PubMed  Google Scholar 

  7. Bauer G (2012) Tumor cell-protective catalase as a novel target for rational therapeutic approaches based on specific intercellular ROS signaling. Anticancer Res 32:2599–2624

    CAS  PubMed  Google Scholar 

  8. Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon ER, Sundaresan M, Finkel T, Goldschmidt-Clermont PJ (1997) Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science 275:1649–1652

    Article  CAS  PubMed  Google Scholar 

  9. Herdener M, Heigold S, Saran M, Bauer G (2000) Target cell-derived superoxide anions cause efficiency and selectivity of intercellular induction of apoptosis. Free Radic Biol Med 29:1260–1271

    Article  CAS  PubMed  Google Scholar 

  10. Bechtel W, Bauer G (2009) Catalase protects tumor cells from apoptosis induction by intercellular ROS signaling. Anticancer Res 29:4541–4557

    CAS  PubMed  Google Scholar 

  11. Heinzelmann S, Bauer G (2010) Multiple protective functions of catalase against intercellular apoptosis-inducing ROS signaling of human tumor cells. Biol Chem 391:675–693. doi:10.1515/bc.2010.068

    Article  CAS  PubMed  Google Scholar 

  12. Lau D, Baldus S (2006) Myeloperoxidase and its contributory role in inflammatory vascular disease. Pharmacol Ther 111:16–26. doi:10.1016/j.pharmthera.2005.06.023

    Article  CAS  PubMed  Google Scholar 

  13. Pabalan N, Jarjanazi H, Sung L, Li H, Ozcelik H (2012) Menopausal status modifies breast cancer risk associated with the myeloperoxidase (MPO) G463A polymorphism in Caucasian women: a meta-analysis. PLoS ONE 7:e32389. doi:10.1371/journal.pone.0032389

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Qin X, Deng Y, Zeng Z-Y, Peng Q-L, Huang X-L, Mo C-J, Li S, Zhao J-M (2013) Myeloperoxidase polymorphism, menopausal status, and breast cancer risk: an update meta-analysis. PLoS ONE 8:e72583. doi:10.1371/journal.pone.0072583

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Yuzhalin AE, Kutikhin AG (2012) Common genetic variants in the myeloperoxidase and paraoxonase genes and the related cancer risk: a review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 30:287–322. doi:10.1080/10590501.2012.731957

    Article  CAS  PubMed  Google Scholar 

  16. Klebanoff SJ, Coombs RW (1991) Viricidal effect of Lactobacillus acidophilus on human immunodeficiency virus type 1: possible role in heterosexual transmission. J Exp Med 174:289–292

    Article  CAS  PubMed  Google Scholar 

  17. Martin HL, Richardson BA, Nyange PM, Lavreys L, Hillier SL, Chohan B, Mandaliya K, Ndinya-Achola JO, Bwayo J, Kreiss J (1999) Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 180:1863–1868. doi:10.1086/315127

    Article  CAS  PubMed  Google Scholar 

  18. He C, Tamimi RM, Hankinson SE, Hunter DJ, Han J (2009) A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk. Breast Cancer Res Treat 113:585–594. doi:10.1007/s10549-008-9962-z

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Lahiri DK, Nurnberger JI Jr (1991) A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 19:5444

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Chu H, Wang M, Wang M, Gu D, Wu D, Zhang Z, Tang J, Zhang Z (2010) The MPO -463G > A polymorphism and cancer risk: a meta-analysis based on 43 case-control studies. Mutagenesis 25:389–395. doi:10.1093/mutage/geq018

    Article  CAS  PubMed  Google Scholar 

  21. Mustea A, Heinze G, Sehouli J, Koensgen D, Wolf A, Gutu L, Sofroni D, Pirvulescu C, Braicu EI, Schuster E, Zeillinger R, Tong D (2007) The -463G/A polymorphism in myeloperoxidase gene and cervical cancer. Anticancer Res 27:1531–1535

    CAS  PubMed  Google Scholar 

  22. Bauer G (2001) Lactobacilli-mediated control of vaginal cancer through specific reactive oxygen species interaction. Med Hypotheses 57:252–257. doi:10.1054/mehy.2000.1285

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the Instituto de Investigação Científica Bento da Rocha Cabral for financial support.

Conflict of interest

The authors declare that they have no conflict of interests.

Author information

Authors and Affiliations

  1. Genetics Laboratory and Environmental Health Institute, Faculty of Medicine, University of Lisbon, Avenida Prof. Egas Moniz, 1649-028, Lisbon, Portugal

    Cindy Castelão, Alda Pereira da Silva, Andreia Matos, Manuel Bicho & Maria Clara Bicho

  2. Dermatology Research Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Lisbon, Portugal

    Cindy Castelão & Maria Clara Bicho

  3. Faculty of Sciences, University of Lisbon, Lisbon, Portugal

    Ângela Inácio

  4. Instituto de Investigação Científica Bento Rocha Cabral, Lisbon, Portugal

    Manuel Bicho

  5. Molecular Oncology Group, Portuguese Institute of Oncology Porto Centre, Porto, Portugal

    Rui Medeiros

Authors
  1. Cindy Castelão
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alda Pereira da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andreia Matos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ângela Inácio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Manuel Bicho
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rui Medeiros
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maria Clara Bicho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cindy Castelão.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Castelão, C., da Silva, A.P., Matos, A. et al. Association of myeloperoxidase polymorphism (G463A) with cervix cancer. Mol Cell Biochem 404, 1–4 (2015). https://doi.org/10.1007/s11010-015-2359-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-015-2359-5

Keywords

Search

Navigation