Polymorphism at the -308-promoter position of the tumor necrosis factor-alpha (TNF-alpha) gene and cervical cancer.

摘要

The purpose of the study was to investigate the hypothesis that the genetically programmed ability to produce low, medium, or high levels of tumor necrosis factor-alpha (TNF-alpha), as determined by TNF-alpha promoter polymorphism at position 308, influenced the development of cancer of the uterine cervix. The population was recruited from patients attending gynecological clinics at two teaching hospitals in Harare, Zimbabwe. Laboratory tests were performed in the Departments of Immunology and Medical Microbiology, Medical School, University of Zimbabwe. One hundred and three patients with invasive cancer of the uterine cervix and 101 healthy women were included in the study. All patients and healthy controls were from the Shona ethnic groups that inhabit northern Zimbabwe. DNA was purified from cervical cytobrush samples obtained from women with cervical cancer. In random cases a second DNA sample was extracted from patient blood. Control DNA was extracted from urine or peripheral blood samples from the healthy women. Detection of allele A and /or G at the 308 position in the promoter region of the TNF-alpha gene was carried out using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. Polymorphism in the amplified products was detected by gel electrophoresis. There was no statistically significant difference in the distribution of the low (G) or high (A) producer alleles at position 308 of the TNF-alpha gene between patients with cervical cancer and healthy women. The high producer haplotype AA was identified in only one patient with cervical cancer and two healthy women. These data suggest that the genetically acquired ability to produce higher levels of TNF-alpha is present in a minority of women with or without cervical cancer in the Zimbabwean population. Homozygosity for allele 308A is very rare. High-producer allele 308A as well as high-producer haplotypes AA is significantly less common in a Zimbabwean population than in a European population.