title: The role of CYBA (p22phox) and catalase genetic polymorphisms and their possible epistatic interaction in cervical cancer.
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.
authors.affiliation: Genetics Laboratory and Environmental Health Institute, Faculty of Medicine, University of Lisbon, Avenida Prof. Egas Moniz, 1649-028, Lisbon, Portugal, nany.castaldo@gmail.com.
authors.forename: Stephanie Anais
authors.initials: SA
authors.lastname: Castaldo
authors.forename: Alda Pereira
authors.initials: AP
authors.lastname: da Silva
authors.forename: Andreia
authors.initials: A
authors.lastname: Matos
authors.forename: Ângela
authors.initials: Â
authors.lastname: Inácio
authors.forename: Manuel
authors.initials: M
authors.lastname: Bicho
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.forename: Irina
authors.initials: I
authors.lastname: Alho
authors.forename: Maria Clara
authors.initials: MC
authors.lastname: Bicho
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics; D002374:Catalase / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D019255:NADPH Oxidases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D017382:Reactive Oxygen Species; D002374:Catalase; D019255:NADPH Oxidases; C086986:CYBA protein, human