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Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea.

ABSTRACT: To investigate associations between the tumor necrosis factor alpha (TNF-?) -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A polymorphisms and HCC in Korea.Hepatocellular carcinoma (HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-? polymorphisms and HCC was analyzed in 157 HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-? polymorphisms, which are TNF-? -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A. The TNF-? genotype frequencies, genotype combinations and haplotypes were analyzed to disclose the association with HCC.None of the TNF-? polymorphisms was significantly associated with HCC. However, nine genotype combinations had associations with increased likelihood of HCC. Among them, TNF-? -1031/-857/-238 TT/CC/GA (AOR = 18.849, 95%CI: 2.203-161.246, P = 0.007), TNF-? -1031/-308/-238 TT/GG/GA (AOR = 26.956, 95%CI: 3.071-236.584, P = 0.003), and TNF-? -1031/-238 TT/GA (AOR = 21.576, 95%CI: 2.581-180.394, P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-? polymorphisms which were significantly associated with HCC. They are TNF-? -1031/-863/-857/-308/-238 T-C-C-G-A (OR = 25.824, 95%CI: 1.491-447.223, P = 0.0005), TNF-? -1031/-857/-308/-238 T-C-G-A (OR = 12.059, 95%CI: 2.747-52.950, P < 0.0001), TNF-? -1031/-857/-238 T-C-A (OR = 10.696, 95%CI: 2.428-47.110, P = 0.0001), TNF-? -1031/-308/-238 T-G-A (OR = 7.556, 95%CI: 2.173-26.280, P = 0.0002) and TNF-? -1031/-238 T-A (OR = 10.865, 95%CI: 2.473-47.740, P = 0.0001). Moreover, HCC Okuda stage III cases with the TNF-? -1031 CC genotype had better survival than those with the TT genotype (AOR = 5.795, 95%CI: 1.145-29.323).Although no single TNF-? polymorphism is associated with HCC in this study, some TNF-? genotype combinations and haplotypes are associated with HCC. In addition, HCC Okuda stage III cases with the TNF-? -1031 TT genotype may have a better prognosis than those with the CC genotype.

SUBMITTER: Shin SP

PROVIDER: S-EPMC4674724 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea.

Shin Suk Pyo SP Kim Nam Keun NK Kim Ju Hwan JH Lee Ju Ho JH Kim Jung Oh JO Cho Sung Hwan SH Park Hana H Kim Mi Na MN Rim Kyu Sung KS Hwang Seong Gyu SG

World journal of gastroenterology 20151201 46

<h4>Aim</h4>To investigate associations between the tumor necrosis factor alpha (TNF-α) -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A polymorphisms and HCC in Korea.<h4>Methods</h4>Hepatocellular carcinoma (HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157 HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigate ...[more]

PMID: 26672513

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Project description:PurposeThis meta-analysis was performed to clarify the association between tumor necrosis factor alpha (TNF-α) gene polymorphisms and open angle glaucoma (OAG) risks, and the association between the TNF-α level in aqueous humor (AH) and the risks of glaucoma.MethodsA computerized literature search was performed for the relevant available studies from three databases including PubMed, ISI Web of Science, and Embase. The fixed or random effect model was selected based on the heterogeneity test using the Q test and the I(2) statistic. The associations between TNF-α gene polymorphisms and OAG risks were estimated by calculating pooled odds ratios (ORs) and the 95% confidence interval (CI), while a pooled standardized mean difference with 95% CI was used for the comparison of TNF-α levels in AH between patients with OAG and controls. Publication bias was estimated using Begg's funnel plots and Egger's regression test.ResultsA total of 14 (1,182 cases and 3,003 controls), five (808 cases and 1,039 controls), three (645 cases and 666 controls), and three studies (404 cases and 625 controls) were finally included in the analyses for the associations between TNF-α -308G/A, -857C/T, -863C/A, and -238G/A polymorphisms and the risks of OAG, respectively. The combined results showed that the TNF-α -308G/A gene polymorphism was significantly associated with risks of high-tension glaucoma (A versus G: OR=1.660, 95% CI=1.033-2.667; AA/AG versus GG: OR=1.713, 95% CI=1.10-2.651), but not with normal tension glaucoma or exfoliation glaucoma. Ethnicity-stratified analysis revealed that a significant association also existed in Asians (A versus G: OR=1.947, 95% CI=1.097-3.456; AA/AG versus GG: OR=1.949, 95% CI=1.140-3.332). None of the other polymorphisms was significantly associated with OAG risks. Furthermore, the pooled results of six studies showed that the TNF-α levels in the AH of patients with OAG was higher than that of the control subjects (standardized mean difference=0.517, 95% CI=0.207-0.826, p=0.001). Probability of publication bias was low across all comparisons illustrated by the funnel plots and Egger's test.ConclusionsThis meta-analysis suggests that patients with OAG may have higher TNF-α levels compared with the control subjects, and the TNF-α -308G/A polymorphism is significantly associated with the risks of high-tension glaucoma. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.

Project description:BackgroundTumor necrosis factor α-induced protein 1 (TNFAIP1) is frequently downregulated in cancer cell lines and promotes cancer cell apoptosis. However, its role, clinical significance and molecular mechanisms in hepatocellular carcinoma (HCC) are unknown.MethodsThe expression of TNFAIP1 in HCC tumor tissues and cell lines was measured by Western blot and immunohistochemistry. The effects of TNFAIP1 on HCC proliferation, apoptosis, metastasis, angiogenesis and tumor formation were evaluated by Cell Counting Kit-8 (CCK8), Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL), transwell, tube formation assay in vitro and nude mice experiments in vivo. The interaction between TNFAIP1 and CSNK2B was validated by liquid chromatography-tandem mass spectrometry (LC-MS/MS), Co-immunoprecipitation and Western blot. The mechanism of how TNFAIP1 regulated nuclear factor-kappaB (NF-κB) pathway was analyzed by dual-luciferase reporter, immunofluorescence, quantitative Real-time polymerase chain reaction (RT-qPCR) and Western blot.FindingsThe TNFAIP1 expression is significantly decreased in HCC tissues and cell lines, and negatively correlated with the increased HCC histological grade. Overexpression of TNFAIP1 inhibits HCC cell proliferation, metastasis, angiogenesis and promotes cancer cell apoptosis both in vitro and in vivo, whereas the knockdown of TNFAIP1 in HCC cell displays opposite effects. Mechanistically, TNFAIP1 interacts with CSNK2B and promotes its ubiquitin-mediated degradation with Cul3, causing attenuation of CSNK2B-dependent NF-κB trans-activation in HCC cell. Moreover, the enforced expression of CSNK2B counteracts the inhibitory effects of TNFAIP1 on HCC cell proliferation, migration, and angiogenesis in vitro and in vivo.InterpretationOur results support that TNFAIP1 can act as a tumor suppressor of HCC by modulating TNFAIP1/CSNK2B/NF-κB pathway, implying that TNFAIP1 may represent a potential marker and a promising therapeutic target for HCC.

Dataset Information

Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea.

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Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea.

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