Cytokine gene polymorphisms of TNF, IFN-γ, and IL-12 as potential predictors in the onset of cervical disease in HR HPV-positive women with behavioral risk cofactors

Abstract

Introduction/Objective. The aim of this study was to investigate the distribution of genotypes and alleles of proinflammatory cytokines TNF, IFN-γ, and IL-12 and their effect on the development of a cervical illness and also to determine their associated influence with cofactors in HR HPV-positive women in Serbia. Methods. We have investigated 24 women and based on the cytological findings they were classified into four groups: PAP II, ASCUS, LSIL, and HSIL. Analysis of TNF, IL-12, and IFN-γ polymorphisms was performed using the real-time PCR TaqMan method. Statistical analysis was performed using parametric and non-parametric tests and correlation and multiple regression analysis. Results. Significantly higher frequency of high production-related TNF AA genotype was observed in severe dysplasia. The correlation between TNF gene polymorphism and cervical findings were highly significant. There was a moderate, significant correlation between low production IFN-γ AA genotype and earlier cervical infections. There was a significant correlation between the IL-12 polymorphism of the low production IL-12 AA genotype and cervical lesions. Conclusion. Results of this study show that HSIL is associated with significantly higher frequency of high production TNF AA genotype. It is known that polymorphisms of certain cytokine genes encoding proteins involved in Th1 and Th2 cellular responses may be associated with better or worse prognosis of cervical disease in women with persistent HR HPV infection. Therefore, they may be considered as biomarkers that may have a predictive role in the development of cervical cancer.

Keywords

• cervical cancer
• cofactors
• gene polymorphism
• tnf
• ifn-g
• il-12