TNFR1 promoter -329G/T polymorphism results in allele-specific repression of TNFR1 expression

Sun Kim, Song Mean Moon, Yong Sung Kim, Jae Jung Kim, Ha Jung Ryu, Yeon Jung Kim, Jung Won Choi, Hong Seok Park, Dae Ghon Kim, Hyoung Doo Shin, Mark S. Rutherford, Bermseok Oh, Jong Keuk Lee

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)395-401
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume368
Issue number2
DOIs
StatePublished - Apr 4 2008

Bibliographical note

Funding 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:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • Hepatocellular carcinoma
  • Promoter
  • Single nucleotide polymorphism (SNP)
  • TNFR1

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