TNFR1 promoter -329G/T polymorphism results in allele-specific repression of TNFR1 expression.
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.
Kim
Sun
S
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.
Moon
Song-Mean
SM
Kim
Yong Sung
YS
Kim
Jae-Jung
JJ
Ryu
Ha-Jung
HJ
Kim
Yeon-Jung
YJ
Choi
Jung-Won
JW
Park
Hong-Seok
HS
Kim
Dae-Ghon
DG
Shin
Hyoung-Doo
HD
Rutherford
Mark S
MS
Oh
Bermseok
B
Lee
Jong-Keuk
JK
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*
D047888:Receptors, Tumor Necrosis Factor, Type I