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.

Microenvironment in Vagina as a Key-Player on Cervical Cancer: Interaction of Polymorphic Genetic Variants and Vaginal Microbiome as Co-Factors

“…In a case-control study, we observed a greater risk for developing ICC associated with the homozygote genotype TT of CAT polymorphism C-262 T polymorphism of the CAT gene (OR = 3.03, 95% CI 1.46-6.29, P = 0.003) [31]. Similarly to other cancers types, the T variant of this polymorphism is associated to a decreased enzyme activity, generating high levels of ROS [32][33][34].…”

“…Similarly to other cancers types, the T variant of this polymorphism is associated to a decreased enzyme activity, generating high levels of ROS [32][33][34]. The interaction of CC genotype of p22phox polymorphism and the TT genotype of CAT leads to a higher risk for ICC (OR = 3.95, 95% CI 1.07-14.52, P = 0.032) [31].…”

The Role of Catalase C262T Gene Polymorphism in the Susceptibility and Survival of Cancers

“…The association between the polymorphism of the CAT C262T gene and increased skin cancer risk was also confirmed30 (CT + TTvs CC: OR = 1.19, 95%CI = 1.00–1.41, P = 0.04; CT vs CC: OR = 1.21,95%CI = 1.02–1.44, P = 0.03). Meanwhile, the CAT C262T polymorphism retained its high position for predicting the susceptibility to cervical cancer12 (TT vs CT + CC: OR = 2.85, 95%CI = 1.44–5.65, P = 0.003; TT vs CC: OR = 2.88, 95%CI = 1.41–5.87, P= 0.004; T vs C: OR = 1.96, 95%CI = 1.31–2.93, P = 0.001). However, no evidence of statistical significance could be detected in other cancer types.…”

“…The CAT gene, which is located on chromosome11p13, consists of 12 introns and 13 exons10. There are several single nucleotide polymorphisms (SNPs) identified in the CAT gene, of which the rs1001179 polymorphism (C262T) was the most extensively studied1112. The CAT C262T polymorphism is encoded on the promoter region, influencing transcriptional and splicing regulation13.…”

Catalase C-262T polymorphism and risk of prostate cancer: Evidence from meta-analysis

“…Catalase is an important endogenous antioxidant enzyme that detoxifies hydrogen peroxide to oxygen and water, thus limiting the deleterious effects of reactive oxygen species (ROS) (Goyal and Basak, 2010). Therefore, the CAT plays an important role in substance metabolism, the polymorphism of CAT gene was associated with the development of diseases, for instance, systemic lupus erythematosus (Warchol et al, 2008), chronic obstructive pulmonary disease (Taniguchi et al, 2014), invasive cervical cancer (Castaldo et al, 2014), and prostate cancer (Karunasinghe et al, 2012;Tefik et al, 2013).…”