title: TNFR1 promoter -329G/T polymorphism results in allele-specific repression of TNFR1 expression.
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.
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Laboratory of Genome Research, 388-1 Pungnap-2-Dong, Songpa-Gu, Seoul 138-736, Republic of Korea.
authors.forename: Sun
authors.initials: S
authors.lastname: Kim
authors.forename: Song-Mean
authors.initials: SM
authors.lastname: Moon
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Jae-Jung
authors.initials: JJ
authors.lastname: Kim
authors.forename: Ha-Jung
authors.initials: HJ
authors.lastname: Ryu
authors.forename: Yeon-Jung
authors.initials: YJ
authors.lastname: Kim
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Choi
authors.forename: Hong-Seok
authors.initials: HS
authors.lastname: Park
authors.forename: Dae-Ghon
authors.initials: DG
authors.lastname: Kim
authors.forename: Hyoung-Doo
authors.initials: HD
authors.lastname: Shin
authors.forename: Mark S
authors.initials: MS
authors.lastname: Rutherford
authors.forename: Bermseok
authors.initials: B
authors.lastname: Oh
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics*
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I