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TNF-? -863 polymorphisms and the risk of hepatocellular carcinoma.

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-? (TNF-?) rs1800629 (-308G/A), rs1800630 (-863C/A); interleukin-1B rs1143627 (-31T/C); and transforming growth factor ?1 (TGF-?1) rs1800469 (-509C/T) in a hospital-based study of 772 HCC cases and 852 cancer-free controls. The distribution of the frequency of TNF-? 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-? rs1800630 A allele was 1.839 times higher than that in the group with TNF-? rs1800630 C (P<0.010). These findings suggest that TNF-? rs1800630 may contribute to the risk of HCC, however, these data require further validation.

SUBMITTER: Yang Y

PROVIDER: S-EPMC3438725 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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

Yang Yan Y Qiu Xiao-Qiang XQ Yu Hong-Ping HP Zeng Xiao-Yun XY Bei Chun-Hua CH

Experimental and therapeutic medicine 20111215 3

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, a ...[more]

PMID: 22969921

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Project description:Background and objective: Interleukin (IL)-1 and tumor necrosis factor (TNF)-? are inflammatory cytokines that play an important role in periodontitis, and their genetic variations have been suggested to be associated with increased risk of periodontitis. Focusing on three single nucleotide polymorphisms (SNPs) of IL-1? + 4845, IL-1? + 3954, and TNF-? -863, we aimed to investigate the relationship between periodontitis risk and the polymorphisms of IL-1 ?/? and TNF-? in Koreans.Material and methods: Mouthwash samples from 548 subjects (135 controls without periodontitis, 387 generalized chronic periodontitis patients, and 26 generalized aggressive periodontitis patients) were collected for isolation of genomic DNA. Genotyping of selected SNPs was performed using real-time PCR. Univariable associations between the polymorphisms and periodontitis were assessed by chi-squared test or Fisher's exact test. To evaluate the association after controlling for confounding effects of various risk factors, we stratified the subjects according to the presence or absence of self-reported diseases and employed multiple logistic regression model to adjust for age, smoking status, and oral hygiene indices and behaviors.Results: Significant association of IL-1? + 3954 and TNF-? -863 polymorphisms with periodontitis was observed after adjusting for the confounding risk factors, but not in univariable association analysis. The significant association between genotype CT of IL-1? + 3954 and increased risk of advanced periodontitis was consistently detected regardless of the status of self-reported diseases. In the polymorphism of TNF-? -863, the genotype with minor allele (CA + AA) was significantly associated with periodontitis susceptibility, which was observed only in the subjects with self-reported diseases.Conclusion: The results suggest that genetic variations of IL-1? + 3954 and TNF-? -863 are associated with increased risk of periodontitis in Koreans. In addition, our findings underscore the importance of controlling for confounding risk factors to detect significant association between genetic factors and risk of periodontitis. A further well-designed large-scale study is needed to warrant our results.

Project description:To investigate the associiations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma (HCC).We enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospital of Guangxi Medical University and 1200 non-tumor patients from the First Affiliated Hospital of Guangxi Medical University. General demographic characteristics, behavioral information, and hematological indices were collected by unified questionnaires. Genomic DNA was isolated from peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom MassARRAY iPLEX genotyping method. The association between genetic polymorphisms and risk of HCC was shown by P-value and the odd ratio (OR) with 95% confidence interval (CI) using the unconditional logistic regression after adjusting for age, sex, nationality, smoking, drinking, family history of HCC, and hepatitis B virus (HBV) infection. Moreover, stratified analysis was conducted on the basis of the status of HBV infection, smoking, and alcohol drinking.The HCC risk was lower in patients with the MCM4 rs2305952 CC (OR = 0.22, 95%CI: 0.08-0.63, P = 0.01) and with the CHEK1 rs515255 TC, TT, TC/TT (OR = 0.73, 95%CI: 0.56-0.96, P = 0.02; OR = 0.67, 95%CI: 0.46-0.97, P = 0.04; OR = 0.72, 95%CI: 0.56-0.92, P = 0.01, respectively). Conversely, the HCC risk was higher in patients with the KAT2B rs17006625 GG (OR = 1.64, 95%CI: 1.01-2.64, P = 0.04). In addition, the risk was markedly lower for those who were carriers of MCM4 rs2305952 CC and were also HBsAg-positive and non-drinking and non-smoking (P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBsAg-negative and non-drinking (P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2B rs17006625 GG and were also HBsAg-negative (P < 0.05).Of 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2B polymorphisms may be associated with the risk of HCC.

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TNF-? -863 polymorphisms and the risk of hepatocellular carcinoma.

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

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