Tumor Biology

, Volume 36, Issue 2, pp 909–914 | Cite as

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

  • Stephanie Anais Castaldo
  • Alda Pereira da Silva
  • Andreia Matos
  • Ângela Inácio
  • Manuel Bicho
  • Rui Medeiros
  • Irina Alho
  • Maria Clara Bicho
Research Article

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.

Keywords

Oxidative stress Cervical cancer CYBA (p22phox) Catalase Polymorphism 

Notes

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.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Stephanie Anais Castaldo
    • 1
    • 2
  • Alda Pereira da Silva
    • 1
  • Andreia Matos
    • 1
  • Ângela Inácio
    • 1
    • 3
  • Manuel Bicho
    • 1
    • 3
  • Rui Medeiros
    • 4
  • Irina Alho
    • 5
  • Maria Clara Bicho
    • 1
    • 2
  1. 1.Genetics Laboratory and Environmental Health Institute, Faculty of MedicineUniversity of LisbonLisbonPortugal
  2. 2.Dermatology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de LisboaLisbonPortugal
  3. 3.Instituto de Investigação Científica Bento da Rocha CabralLisbonPortugal
  4. 4.Molecular Oncology Group, Portuguese Institute of Oncology, Porto CentrePortoPortugal
  5. 5.Clinical and Translational Oncology Research Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de LisboaLisbonPortugal

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