Abstract
BackgroundCervical cancer is due to infection with specific high-risk types of human papillomavirus (HPV). Although the incidence of genital HPV infection in various population groups is high, most of these regress without intervention. Investigating genetic host factors and cellular immune responses, particularly cytokines, could help to understand the association between genital HPV infection and carcinogenesis. The tumor necrosis factor alpha (TNF-α) cytokine plays an important role in all stages of cervical cancer and has the ability to induce the regression of human tumors. Therefore the aim of the study was to investigate the allelic distribution of -308 TNF-α gene polymorphism in South African women with cervical cancer compared to control women.MethodsIncluded in our study were women with histologically proven cancer of the cervix (n = 244) and hospital-based controls (n = 228). All patients and controls were from mixed race and black population groups in South Africa. The detection of a bi-allelic -308 (A/G) polymorphism in the promoter region of TNF-α was investigated using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The distributions of the allelic frequencies were stratified in both patients and controls into two South African ethnic population groups.ResultsIn this study we observed no association between the distribution of -308 TNF-α polymorphism and the risk of developing cervical cancer even after combining the data from the two ethnic populations (X2 = 2.26). In addition, using the chi-squared test we found no significant association between the known risk factors for cervical cancer and the allele distribution of -308 TNF-α. However, the frequency of the rare high-producing allele -308A of TNF-α was significantly lower in the South African population when compared to Caucasians and Chinese population groups.ConclusionWe demonstrated no association between -308 TNF-α polymorphism and the risk of cervical cancer among two South African ethnic population groups. However, as the distribution of the -308A TNF-α was notably different between the control groups of South Africa and other population groups this result suggests that ethnic disparity may influence the levels of TNF-α produced.
Highlights
Cervical cancer is due to infection with specific high-risk types of human papillomavirus (HPV)
There were no significant differences in the distribution of TNF-α allelic polymorphisms and the risk of developing cervical cancer in the mixed race group, (OR, 2.93; 95% CI, 0.51–16.72) or the black group (OR, 0.87; 95% CI, 0.27–2.76)
As there were no significant differences in the distribution of the -308 TNF-α alleles in the cervical cancer patients among the two South African ethnic populations, the data was combined to compare allele distributions to other population groups (Table 2)
Summary
Cervical cancer is due to infection with specific high-risk types of human papillomavirus (HPV). The incidence of genital HPV infection in various population groups is high, most of these regress without intervention. Investigating genetic host factors and cellular immune responses, cytokines, could help to understand the association between genital HPV infection and carcinogenesis. The tumor necrosis factor alpha (TNF-α) cytokine plays an important role in all stages of cervical cancer and has the ability to induce the regression of human tumors. There is strong epidemiological and experimental data that have demonstrated a definite association of high-risk human papillomavirus (HR-HPV) infection and the development of cervical cancer [1]. An effective host immune response may be an important determinant for the persistence and progression of HPV induced cervical cancer. CMI is regulated by cytokines that are secreted primarily by T helper (Th) cells and macrophages
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