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 tumor necrosis factor alpha (TNF-alpha) promoter region are associated with endometrial cancer. TNF-alpha gene encodes a cytokine involved in angiogenesis and oncogenesis of several cancers. Some uncommon alleles are reported to be associated with increased production of TNF-alpha and the onset of various cancers. Studies of such alleles are lacking in endometrial cancer. In this study, we examined the genetic changes at the polymorphic 3 loci of TNF-alpha promoter regions (-238, -308 and 488) in 41 Japanese patients with uterine endometrial carcinomas (UEC). Nine of 41 UEC samples (22%) had genotype changes from GA to A at -308 promoter region of the TNF-alpha gene. There were no genotype changes at -238 and 488 regions of TNF-alpha in UEC samples. The results of our study demonstrate for the first time that genotype changes from GA to A in UEC patients. We conclude that the genotype changes at -308 promoter region of TNF-alpha may play an essential role in the malignant transformation of endometrial cells.
Sasaki
M
M
Department of Urology (112F), University of California San Francisco and VA Medical Center, San Francisco, CA 94121, USA.
Nakajima
K
K
Perinchery
G
G
Fujino
T
T
Oh
B R
BR
Fujimoto
S
S
Dahiya
R
R
D002471:Cell Transformation, Neoplastic; D016889:Endometrial Neoplasms / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha