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

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

Sexta, 28.11.2014

A infecção pelo Papilomavírus Humano (HPV) é necessária, mas não suficiente, para o desenvolvimento do cancro do colo do útero. É bastante importante a participação de vários factores no processo de infecção, transformação e imortalização celular. O papel das espécies reactivas de oxigénio (ROS) em tumores é cada vez mais conhecido, promovendo a carcinogénese e a sinalização celular e metastática. Assim,o principal objectivo deste trabalho foi estudar polimorfimos em genes chave no sistema redox de maneira a identificar novos factores de risco genéticos para o desenvolvimento de carcinoma invasivo do colo do útero. O trabalho publicado foi desenvolvido aquando da tese de Mestrado da autora. Actualmente, o encontra-se sob o abrigo de uma bolsa de investigação no Centro de Biomedicina Molecular e Estrutural (CBME) na Universidade do Algarve, e seu trabalho foca-se no estudo do papel da proteína Anexina A2 na sinalização dependente de espécies reactivas de oxigénio em células cancerígenas, sob orientação da Doutora Patrícia Madureira.

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 Genetics Laboratory and Environmental Health Institute, Faculty of Medicine, University of Lisbon, Portugal

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

3 Instituto de Investigação Científica Bento da Rocha Cabral, Lisboa, Portugal

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

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

HPV infection is necessary but not a sufficient cause for the development of invasive cervix 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 (χ2 test: p= 0.017 and p= 0.009, respectively). Women with the C/T CYBA-242 genotype had a lower risk for ICC development (OR= 0.515, 95% 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, cervix cancer, CYBA (p22phox), catalase, polymorphism

Revista: Tumor Biology

http://link.springer.com/article/10.1007/s13277-014-2714-2