1. TNFR1 promoter -329G/T polymorphism results in allele-specific repression of TNFR1 expression.
- Author
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Kim S, Moon SM, Kim YS, Kim JJ, Ryu HJ, Kim YJ, Choi JW, Park HS, Kim DG, Shin HD, Rutherford MS, Oh B, and Lee JK
- Subjects
- Cell Line, Tumor, Down-Regulation, Gene Expression Regulation, Neoplastic, Gene Frequency genetics, Genetic Predisposition to Disease genetics, Humans, Promoter Regions, Genetic genetics, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Liver Neoplasms genetics, Liver Neoplasms metabolism, Polymorphism, Single Nucleotide genetics, Receptors, Tumor Necrosis Factor, Type I genetics
- Abstract
Tumor necrosis factor (TNF) and the TNF receptor (TNFR) superfamily play very important roles for cell death as well as normal immune regulation. Dysregulation of TNF-TNFR superfamily gene expression will influence many biological processes, and contributes to human diseases, including cancer. We investigated the genetic alterations of the TNF-TNFR superfamily genes in hepatocellular carcinoma (HCC). Several genetic alterations were detected in the 44 TNF-TNFR superfamily genes by sequencing hepatocellular carcinoma DNA samples. In particular, we found that the TNFR1 promoter -329G/T polymorphism was strongly associated with primary HCC (odds ratio [OR]=5.22, p=0.0007). We also observed frequent loss of heterozygosity at the polymorphic TNFR1 -329G/T site in the primary tumor tissues, indicating that the polymorphic TNFR1 -329G/T site is very susceptible to genetic alterations in HCC. Furthermore, in the polymorphic TNFR1 -329G/T site, the T allele resulted in the repression of TNFR1 expression. Therefore, our results suggest that TNFR1 -329G/T polymorphism may play an important role in the development of HCC.
- Published
- 2008
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