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.
The purpose of this study was to characterise the prevalence and risk factors associated with genital mycoplasmas ( Mycoplasma hominis [MH], M. genitalium [MG]) and ureaplasmas ( Ureaplasma urealyticum [UU], U. parvum [UP]) in Portuguese women of reproductive age. The cross-sectional study included 612 cervicovaginal self-collected samples from women aged 15-44 years, tested for MH, MG, UU, UP by polymerase chain reaction. Y chromosome (Yc) DNA was detected as a biomarker of recent unprotected sexual intercourse. The prevalences of UU, UP, MH and MG were 28.4% (95% confidence interval [CI] 25.0-32.1), 22.4% (95% CI 19.3-25.9), 8.5% (95% CI 6.5-11.0) and 0.8% (95% CI 0.4-1.9), respectively. Overall, women aged 20-29 years (odds ratio [OR] 1.78; P = 0.010) and the presence of Yc-DNA (OR 2.33; P = 0.038) were associated with an increased risk of UU. Lifetime number of sexual partners was a predictor of UU, UP and MH (OR 2.46; P < 0.001, OR 2.78; P < 0.001 and OR 1.55; P < 0.001, respectively, for more than one versus one partner). The prevalence of MG was low, while UU, UP and MH were common in Portuguese women of reproductive age. The presence of UU, UP and MH was associated with sexual activity (number of sexual partners), although the consequences of its prevalence are not fully understood and should be further investigated.
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