Molecular Evaluation of TNF-α-308 and TNF-α-238 Polymorphisms and their Association with HPV Genotypes in Cervical Lesions

Abstract

Abstract Background: Cervical cancer is a multi-stage disease that is contaminated by a DNA virus and is involved in one or more stages in the pathogenesis process. In addition to human papillomaviruses (HPV), the tumor necrosis factor-α gene (TNF-α) is considered a major intermediate mediator of the acute inflammatory response to viruses and a gram-negative bacterium. The pro-region polymorphisms of the TNF-α gene such as -308 and -238 polymorphisms affect the expression of this gene. Therefore, this study aimed to investigate the polymorphisms of the TNF-α gene and its relationship with various genotypes of HPV in cervical lesions. Methods: In this study, 58 female patients with cervical cancer symptoms were selected, then following histopathologic studies, DNA was extracted from all specimens, and the PCR method was used to determine the types of HPV genotypes and TNF-α gene polymorphisms. Also, an ARMS-PCR reaction was performed to amplify TNF-α -308 and TNF-α -238 polymorphisms. Statistical analysis of the data was carried out by the Epi Info software version 7. 2 and Chi-Square (x2) test using SPSS ver.7.3.1.10. These lesions were categorized into metaplasia groups (93.37%), cervical intraepithelial neoplasia (CIN) I and II (20.68%), CIN III (15.51%) and squamous cell carcinoma (SCC) (25.86%). Results: In this study 58 lesions were collected and 26 of which were HPV positive. They were categorized as the following: 1 sample (4.53%) metaplasia, 7 samples (33.58%) CIN I and CIN II, 6 samples (66.66%) CIN III and 12 samples (80%) SCC. According to the results of statistical analysis, there was a significant difference between different types of HPV genotypes in different wastes. On the other hand, in contrast to the -238 polymorphism of the TNF-α gene, a significant difference was observed between the various types of -308 polymorphism of the TNF-α gene in the three groups of metaplasia, CIN, and SCC. In general, we can conclude that GG genotype testing of the -308 polymorphism of TNF-α gene and HPV types in combination with para-clinical parameters can be effective as risk factors and molecular markers for prognosis and early treatment of cervical cancer.