Frequent genotype changes at-308 of the human tumor necrosis factor-alpha promoter region in human uterine endometrial cancer

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.