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.
|Original language||English (US)|
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Apr 4 2008|
Bibliographical noteFunding Information:
The authors are grateful to Dr. A. Fujiyama (RIKEN Genomic Sciences Center, Japan) for the provision of sample supplies (chimpanzee DNA). This work was supported in part by a Grant (#0720200) of the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea and a Grant (#07-419) from the Asan Institute for Life Sciences, Seoul, Korea.
Copyright 2008 Elsevier B.V., All rights reserved.
- Hepatocellular carcinoma
- Single nucleotide polymorphism (SNP)