Increased Risk of Developing Hepatocellular Carcinoma Associated with Carriage of the TNF2 Allele of the -308 Tumor Necrosis Factor-α Promoter Gene

Ho, Sheng Yow; Wang, Ying Jan; Chen, Hen Li; Chen, Chih‐Hung; Chang, Chih Jen; Wang, Po Jen; Chen, Helen H.W.; Guo, How‐Ran

doi:10.1023/b:caco.0000036173.99930.75

Cited by 67 publications

(43 citation statements)

References 32 publications

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“…In a study by Kakumu et al TNF-αRs correlated with disease progression and IFN-α treatment did not affect their level (162). Regardin TNF-α polymorphism, the TNF-α (-308) SNP (single nucleotide polymorphisms) in the promoter region of the gene, which includes TNF-α1 (-308G) and TNF-α2 (-308A) alleles, is associated with cancer susceptibility and induced expression of TNF-α (153,(165)(166)(167).…”

Section: Hepatic Stellate Cells (Hscs)mentioning

confidence: 99%

The tumor microenvironment in hepatocellular carcinoma (Review)

et al. 2012

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Abstract. The tumor microenvironment has been largely studied as a dynamic system orchestrated by inflammatory cells, including cancer cells, stroma as well as the extracellular matrix. It is useful to describe and predict the phenotypic characteristics of cancer. Furthermore, a better understanding of its interplay with the various aspects of the tumor cells may be utilized for the discovery of novel molecular targets. Liver cancer is considered a model of the relation occurring between the tumor microenvironment and tumor development. The chronic inflammatory status of the liver, sustained by the infection of hepatitis viruses, as well as the production of cytokines and growth factors within the parenchyma, lead to an intricate microenvironment. The identification of novel molecular therapeutic targets may improve the outcome of patients with liver cancer as it remains the third leading cause of cancer death worldwide. In the present study, the tumor microenvironment in hepatocellular carcinoma (HCC) was explored by a review of the literature. Studies on hepatitis virus infections and the consequent chronic inflammatory status were examined. In this context, immune-mediated and/or virusrelated molecular mechanisms have been hypothesized as being responsible for liver cancer development. The interlink among HCC microenvironment components, comprising cellular elements, cytokines, growth factors and several proteins is also described together with the role of matrix metalloproteinases in HCC development. Finally, the rationale for targeting tumorstromal interface is summarized in the context of new therapeutic opportunities.

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Section: Hepatic Stellate Cells (Hscs)mentioning

confidence: 99%

The tumor microenvironment in hepatocellular carcinoma (Review)

et al. 2012

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“…The etiological factors involved in HCC are well known (Ho et al 2004), but genetic factors of HCC have been incompletely understood, which has been postulated to inXuence the progression of HCC. Because risk for HCC increases with the severity of hepatic inXammation and chronic inXammation developing through the action of various inXammatory mediators is known as a cofactor of carcinogenesis (Coussens andWerb 2002, Tarao et al 1999), among inXammatory mediators, pro-inXammatory cytokine, TNF-has been postulated to have a crucial role in the pathogenesis of cancers.…”

Section: Introductionmentioning

confidence: 99%

The TNF-α, IL-1B and IL-10 polymorphisms and risk for hepatocellular carcinoma: a meta-analysis

Luo

Feng

et al. 2010

J Cancer Res Clin Oncol

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“…In a case study in Taiwan, the authors concluded that carrying the TNF2 allele is a significant predictor of HCC independent of hepatitis B and C, and therefore that it may be used as a biomarker for susceptibility to HCC (12). Several polymorphisms of proinflammatory IL-1Β have been reported, and the IL-1B-31 the IL-1B-511 genotypes have been associated with enhanced IL-1B production.…”

Section: Tnf-α -863 Polymorphisms and The Risk Of Hepatocellular Carcmentioning

confidence: 99%

TNF-α -863 polymorphisms and the risk of hepatocellular carcinoma

Yang

Qiu

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Hepatocellular carcinoma (HCC) is a common type of highly malignant tumor. Guangxi is an area of China characterized by a high incidence of HCC. Previous epidemiological studies have found that chronic infection with hepatitis B virus (HBV) is one of the major etiological risk factors for HCC in China. With the increased understanding of the host immune response against HBV and the pathogenesis of the virus, at present, greater attention is being given to the immune response of cytokine genes, as polymorphisms may have a major impact on the course and outcome of HBV infection. In the present study, we genotyped tumor necrosis factor-α (TNF-α) rs1800629 (-308G/A), rs1800630 (-863C/A); interleukin-1B rs1143627 (-31T/C); and transforming growth factor β1 (TGF-β1) rs1800469 (-509C/T) in a hospital-based study of 772 HCC cases and 852 cancer-free controls. The distribution of the frequency of TNF-α rs1800630 sites of CC, CA, AA were 65.67, 27.46 and 6.87% in the case group, respectively, as compared with 67.02, 29.58 and 3.40% in the controls, all with a statistical significance (P<0.05). The logistic regression analysis revealed that the variant rs1800630 AA genotypes were associated with a significantly increasing risk of HCC (OR=2.058, 95% CI 1.289-3.287), compared with the wild-type rs1800630 CC. Further stratified analyses showed that after stratification for history of alcohol drinking, in a subgroup of individuals without a history of drinking, the HCC risk in the group with the TNF-α rs1800630 A allele was 1.839 times higher than that in the group with TNF-α rs1800630 C (P<0.010). These findings suggest that TNF-α rs1800630 may contribute to the risk of HCC, however, these data require further validation. IntroductionHepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third most common cause of death from cancer. It is estimated that the number of new cases worldwide is 626,000 and deaths from liver cancer reached 598,000 in the year 2002 (1). An estimated 711,000 cases of primary liver cancer occurred worldwide in 2007; approximately three-quarters of these cases were HCC. More than 80% of cases occurred in developing countries; >55% occurred in China alone (2). Guangxi is an area in China characterized by a high incidence of HCC, and the statistical data indicate that in the period 2004-2005, the crude mortality from primary liver cancer was 34.39/100,000 individuals in Guangxi Province (3).Previous epidemiological studies have found that chronic infection with hepatitis B virus (HBV) is one of the major etiological risk factors for HCC in China (4,5). Chronic HBV infection is an important cause of HCC in China and >90% of patients with HCC are associated with HBV infection (6). After initial infection with HBV, 90-95% of adults can rely on their own immune systems to clear the virus which presents as self-limiting hepatitis. Only 5-10% of those infected develop chronic hepatitis, and 10-25% of these patients eventually progress to HCC (7,8). This suggests that the bod...

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Increased Risk of Developing Hepatocellular Carcinoma Associated with Carriage of the TNF2 Allele of the -308 Tumor Necrosis Factor-α Promoter Gene

Abstract: Carriage of the TNF2 allele is a significant predictor of HCC independent of hepatitis B and C, and therefore it may be used as a biomarker for susceptibility to HCC.

Cited by 67 publications

References 32 publications

The tumor microenvironment in hepatocellular carcinoma (Review)

The tumor microenvironment in hepatocellular carcinoma (Review)

The TNF-α, IL-1B and IL-10 polymorphisms and risk for hepatocellular carcinoma: a meta-analysis

TNF-α -863 polymorphisms and the risk of hepatocellular carcinoma

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