M. Sasaki et al., Frequent genotype changes at-308 of the human tumor necrosis factor-alpha promoter region in human uterine endometrial cancer, ONCOL REP, 7(2), 2000, pp. 369-373
This study was designed to test the hypothesis that genotypic changes of tu
mor necrosis factor alpha (TNF-alpha) promoter region are associated with e
ndometrial cancer. TNF-alpha gene encodes a cytokine involved in angiogenes
is and oncogenesis of several cancers. Some uncommon alleles are reported t
o be associated with increased production of TNF-alpha and the onset of var
ious cancers. Studies of such alleles are lacking in endometrial cancer. In
this study, we examined the genetic changes at the polymorphic 3 loci of T
NF-alpha promoter regions (-238, -308 and 488) in 41 Japanese patients with
uterine endometrial carcinomas (UEC). Nine of 41 UEC samples (22%) had gen
otype changes from GA to A at -308 promoter region of the TNF-alpha gene. T
here were no genotype changes at -238 and 488 regions of TNF-alpha in UEC s
amples. The results of our study demonstrate for the first time that genoty
pe changes from GA to A in UEC patients. We conclude that the genotype chan
ges at -308 promoter region of TNF-alpha may play an essential role in the
malignant transformation of endometrial cells.