The allelic distribution of -308 Tumor Necrosis Factor-alpha gene polymorphism in South African women with cervical cancer and control women.
BACKGROUND
Cervical 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-alpha) 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-alpha gene polymorphism in South African women with cervical cancer compared to control women.


METHODS
Included 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-alpha 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.


RESULTS
In this study we observed no association between the distribution of -308 TNF-alpha 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-alpha. However, the frequency of the rare high-producing allele -308A of TNF-alpha was significantly lower in the South African population when compared to Caucasians and Chinese population groups.


CONCLUSIONS
We demonstrated no association between -308 TNF-alpha polymorphism and the risk of cervical cancer among two South African ethnic population groups. However, as the distribution of the -308A TNF-alpha 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-alpha produced.
Govan
Vandana A
VA
Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa. vgovan@curie.uct.ac.za
Constant
Debbie
D
Hoffman
Margaret
M
Williamson
Anna-Lise
AL
D000328:Adult; D016022:Case-Control Studies; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D030361:Papillomavirus Infections / Q000150:complications; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013019:South Africa; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000208:ethnology / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha