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The role of CYBA (p22phox) and catalase genetic polymorphisms and their possible epistatic interaction in cervical cancer

  • Research Article
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Tumor Biology

Abstract

Human papillomavirus (HPV) infection is necessary but not a sufficient cause for the development of invasive cervical cancer (ICC). Epithelial tissues, target for HPV, are exposed to reactive oxygen species (ROS) associated with tumor initiation and progression. The NADPH oxidase (NOX) and catalase (CAT) are involved in hydrogen peroxide (H2O2) production and inactivation, respectively. P22phox is the NOX subunit encoded by the CYBA gene that has a functional polymorphism (C-242T). This protein is involved in the regulation of electron transfer to oxygen. CAT is a hemic enzyme that plays a role in regulating H2O2 concentration, with a functional polymorphism (C-262T) in its gene. We evaluated CYBA C-242T and CAT C262T genetic polymorphisms and their interaction in 132 women with ICC. We found that CYBA C-242T and CAT C262T genotype frequencies were significantly different between ICC and controls (χ 2 test, p = 0.017 and p = 0.009, respectively). Women with the C/T CYBA-242 genotype had a lower risk for ICC development (odds ratio (OR) = 0.515, 95 % confidence interval (CI) 0.291–0.914, p = 0.023) whereas T/T CAT-262 genotype carriers present an increased risk for ICC (OR = 3.034, 95 % CI 1.462–6.298, p = 0.003). Women with C/C genotype for CYBA and T/T genotype for CAT had an increased risk to develop ICC comparing with the interaction of the other possible genotypes of both genes (OR = 3.952, 95 % CI 1.075–14.521, p = 0.032). The CYBA C-242T and CAT C-262T genetic polymorphisms and their epistatic interactions can be associated with ICC through mechanisms related with the role of ROS in cell proliferation and apoptosis.

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References

  1. Muñoz N, Castellsagué X, de González AB, Gissmann L. Chapter 1: HPV in the etiology of human cancer. Vaccine. 2006;31(24 Suppl 3):S3/1–10.

    Google Scholar 

  2. De Marco F. Oxidative stress and HPV carcinogenesis. Viruses. 2013;5(2):708–31.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wu W-S. The signaling mechanism of ROS in tumor progression. Cancer Metastasis Rev. 2006;25(4):695–705.

    Article  CAS  PubMed  Google Scholar 

  4. Laurent A, Nicco C, Chéreau C, Goulvestre C, Alexandre J, Alves A, et al. Controlling tumor growth by modulating endogenous production of reactive oxygen species. Cancer Res. 2005;65(3):948–56.

    CAS  PubMed  Google Scholar 

  5. Bechtel W, Bauer G. Catalase protects tumor cells from apoptosis induction by intercellular ROS signaling. Anticancer Res. 2009;29(11):4541–57.

    CAS  PubMed  Google Scholar 

  6. Bechtel W, Bauer G. Modulation of intercellular ROS signaling of human tumor cells. Anticancer Res. 2009;29(11):4559–70.

  7. Bauer G. Targeting extracellular ROS signaling of tumor cells. Anticancer Res. 2014;34(4):1467–82.

    CAS  PubMed  Google Scholar 

  8. Lambeth JD. Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy. Free Radic Biol Med. 2007;43(3):332–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sardina JL, López-Ruano G, Sánchez-Abarca LI, Pérez-Simón JA, Gaztelumendi A, Trigueros C, et al. p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation. Cell Death Differ. 2010;17(12):1842–54.

    Article  CAS  PubMed  Google Scholar 

  10. Ushio-fukai M, Zafari AM, Fukui T, Ishizaka N, Griendling KK. p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells*. J Biol Chem. 1996;271(38):23317–21.

    Article  CAS  PubMed  Google Scholar 

  11. Najafi M, Alipoor B, Shabani M, Amirfarhangi A, Ghasemi H. Association between rs4673 (C/T) and rs13306294 (A/G) haplotypes of NAD(P)H oxidase p22phox gene and severity of stenosis in coronary arteries. Gene. 2012;499(1):213–7.

    Article  CAS  PubMed  Google Scholar 

  12. Schreiber R, Ferreira-Sae MC, Ronchi J A, Pio-Magalhães J A, Cipolli J A, Matos-Souza JR, et al. The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients. BMC Med Genet. BioMed Central Ltd; 2011;12(1):114.

  13. Chang D, Hu ZL, Zhang L, Zhao YS, Meng QH, Guan QB, et al. Association of catalase genotype with oxidative stress in the predication of colorectal cancer: modification by epidemiological factors. Biomed Environ Sci. 2012;25(2):156–62.

    CAS  PubMed  Google Scholar 

  14. Chelikani P, Ramana T, Radhakrishnan TM. Catalase: a repertoire of unusual features. Indian J Clin Biochem. 2005;20(2):131–5.

  15. Khodayari S, Salehi Z, Asl SF, Aminian K, Mirzaei Gisomi N, Dalivandan ST. Catalase gene C-262T polymorphism: importance in ulcerative colitis. J Gastroenterol Hepatol. 2013;28(5):819–22.

  16. Matos A, Moutinho J, Pinto D, Medeiros R. The influence of smoking and other cofactors on the time to onset to cervical cancer in a southern European population. Eur J Cancer Prev. 2005;14(5):485–91.

    Article  CAS  PubMed  Google Scholar 

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

  18. Mesquita FS, Dyer SN, Heinrich DA, Bulun SE, Marsh EE, Nowak RA. Reactive oxygen species mediate mitogenic growth factor signaling pathways in human leiomyoma smooth muscle cells. Biol Reprod. 2010;82(2):341–51.

  19. Manda G, Nechifor MT, Neagu T-M. Reactive oxygen species, cancer and anti-cancer therapies. Curr Chem Biol [Internet]. 2009;3(1):342–66.

    Article  CAS  Google Scholar 

  20. Behrend L, Henderson G, Zwacka R. Molecular mechanisms of signalling molecular mechanisms of signalling transformation. Biochem Soc Trans. 2003;31(6):1441–4.

    Article  CAS  PubMed  Google Scholar 

  21. Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004;7(2):97–110.

  22. Guzik TJ, West NEJ, Black E, McDonald D, Ratnatunga C, Pillai R, et al. Functional effect of the C242T polymorphism in the NAD(P)H oxidase p22phox gene on vascular superoxide production in atherosclerosis. 2000;102(15):1744–7.

  23. Wu Z, Lou Y, Jin W, Liu Y, Lu L, Chen Q, et al. Relationship of the p22phox (CYBA) gene polymorphism C242T with risk of coronary artery disease: a meta-analysis. PLoS One. 2013;8(9):e70885.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Comings DE, MacMurray JP. Molecular heterosis: a review. Mol Genet Metab. 2000;71(1–2):19–31.

  25. Fabre E, Raynaud-Simon A, Golmard J, Hebert M, Dulcire X, Succari M, et al. Gene polymorphisms of oxidative stress enzymes: prediction of elderly renutrition. Am J Clin Nutr. 2008;4:1504–12.

    Google Scholar 

  26. Funke S, Risch A, Nieters A, Hoffmeister M, Stegmaier C, Seiler CM, et al. Genetic polymorphisms in genes related to oxidative stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and survival of rectal cancer patients after radiotherapy. J Cancer Epidemiol. 2009;2009:302047.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors would like to thank the Instituto de Investigação Científica Bento da Rocha Cabral for financial support regarding the determination of C-242T CYBA and C-262T CAT genetic polymorphisms.

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Authors and Affiliations

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

    Stephanie Anais Castaldo, Alda Pereira da Silva, Andreia Matos, Ângela Inácio, Manuel Bicho & Maria Clara Bicho

  2. Dermatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal

    Stephanie Anais Castaldo & Maria Clara Bicho

  3. Instituto de Investigação Científica Bento da Rocha Cabral, Lisbon, Portugal

    Ângela Inácio & Manuel Bicho

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

    Rui Medeiros

  5. Clinical and Translational Oncology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal

    Irina Alho

Authors
  1. Stephanie Anais Castaldo
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  2. Alda Pereira da Silva
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  3. Andreia Matos
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  7. Irina Alho
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  8. Maria Clara Bicho
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Correspondence to Stephanie Anais Castaldo.

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Castaldo, S.A., da Silva, A.P., Matos, A. et al. The role of CYBA (p22phox) and catalase genetic polymorphisms and their possible epistatic interaction in cervical cancer. Tumor Biol. 36, 909–914 (2015). https://doi.org/10.1007/s13277-014-2714-2

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  • DOI: https://doi.org/10.1007/s13277-014-2714-2

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