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

Abstract

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...

The phospholipase A2 activity of peroxiredoxin 6 promotes cancer cell death induced by tumor necrosis factor alpha in hepatocellular carcinoma

“…The TNF-a level is increased in the tumor microenvironment of HCC [27]. It regulates HCC carcinogenesis and progression by activating cell apoptosis [28,29]. In this study, we found that PRDX6, with iPLA2 activity, may act as a mediator for TNF-a-induced apoptosis in HCC.…”

Association between five types of Tumor Necrosis Factor-α Gene Polymorphism and Hepatocellular Carcinoma Risk: A Meta-Analysis

“…Polymorphism of TNF-α -863 C/A in the promoter region can in uence TNF-α expression, however, the result is still con icting. Some research suggest that it may increase TNF-α expression [49,50], while other research show the opposite result in which it may decrease TNF-α expression [27,51].…”

“…Each study has sample size ranged from 45 to 1,624 participants. Of all included studies in this metaanalysis, most studies came from Asia, in which 7 studies were from China [7,[22][23][24][25][26][27], 4 from Taiwan [15,[28][29][30], 2 from India [18,31], 2 from Korea [8,32], 1 was Japanese [33], 1 was Thai [34], and 1 was Turkey [35]. There were also some studies with non-Asian countries, including 2 from Egypt [36,37], 1 from Brazil [38], 1 from Italy [39], and 1 from Tunisia [40].…”

Role of Alleles and Genotypes of Polymorphisms of IL-18 (-607 C/A; and -137 C/G), IFN-γ (+874 A/T) and TNF-α (-238 A/G and -308 A/G) and HLA-G Genes in the Susceptibility of Hepatocellular Carcinoma

“…Similarly, Jung et al, studying 227 Korean patients with HCC and 365 controls, detected a higher frequency of allele -238*A among patients with HCC than among healthy controls [47]. On the other hand, Yang et al, did not find statistical difference in TNF-α -308G/ A alleles or genotypes frequencies between Chinese HCC patients (n=772) and healthy controls (n=852), but they observed that TNF-α -863AA genotype may increase the risk of HCC compared with the wild-type TNF-α CC [48].…”