Association between TNF-α, Interleukin-18 Polymorphisms and Risk of Hepatocellular Carcinoma in Egyptian patients.
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ABSTRACT: Objective
To evaluate the association of gene polymorphisms of the SNP of TNF-α gene -238G>A and IL-18 gene-607C>A with the development of hepatocellular carcinoma among Egyptian patients.Methods
One hundred and fifty patients were allocated to this study; eighty patients with hepatocellular carcinoma (Group A), seventy cancer-free HCV age, and sex-matched patients (Group B). We analyzed two Single nucleotide polymorphisms (SNPs) (TNF-α-238G>A and IL-18-607C>A) by real-time polymerase chain reaction using sequence-specific primers (PCR-SSP).Results
Significant higher risk of HCC was associated with genotype IL-18-607AA (p <0.001), OR: 5(2.188-11.47), allele IL-18 -607⁄A (P=0.001), OR: 2.1(1.32-3.3). A significant association was found between the size of HFL in the HCC group and different genotypes of IL18 genes (P=0.013) where 62.5% of patients with tumor size >5 cm carried the risky (AA) genotype on the other hand the SNP of TNF-α gene -238G>A showed no statistically significant association between the two groups.Conclusion
The SNP -607C>A in the IL18 gene was associated with increased HCC risk in Egyptian patients suggesting its use as a potential diagnostic non-invasive tool that allows to identify a new group of HCC patients at an earlier stage.
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SUBMITTER: Sharafelldin H
PROVIDER: S-EPMC8286680 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We investigated the association between interleukin-18 (IL-18) polymorphisms and the susceptibility and clinicopathological state of hepatocellular carcinoma (HCC). In total, 901 participants, including 559 healthy controls and 342 patients with HCC, were recruited. The allelic discrimination of -607A/C (rs1946518) and -137G/C (rs187238) polymorphisms of IL-18 was assessed through real-time polymerase chain reaction by performing the TaqMan assay. The IL-18 -137G/C polymorphism but not the -607A/C polymorphism showed a significant association with the risk of HCC. Participants carrying the IL-18 -137 polymorphism with heterozygous G/C and homozygous CC genotypes showed a 1.987-fold increase (95% CI = 1.301-3.032; p = 0.001) in the risk of HCC compared with those homozygous for wild-type G/G. The 342 patients with HCC carrying the IL-18 -137G/C polymorphism were positive for hepatitis B virus (HBV) infection with an adjusted odds ratio of 1.668. Moreover, the 142 HBV positive patients with HCC and the IL-18 -137 polymorphism were positive for at least one C genotype and showed significant vascular invasion (p = 0.018). Furthermore, the level of ?-fetoprotein was high in the patients carrying the IL-18 -137 polymorphism with GC+CC alleles (p = 0.011). In conclusion, the IL-18 -137G/C polymorphism with a GC+CC genotype could be a factor that increases the risk of HCC. Furthermore, the correlation between the IL-18 -137G/C polymorphism and HCC-related HBV infection is a risk factor for vascular invasion and has a synergistic effect that can further enhance HCC prognosis.
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Project description:BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies occurring worldwide and is most frequent type of liver cancer. The risk for developing HCC increases with the severity of inflammation and fibrosis. The members of the interleukin-1 (IL-1) family are primarily proinflammatory cytokines due to their ability to stimulate the expression of genes associated with inflammation and autoimmune diseases. Several studies have suggested that some proinflammatory cytokines, such as the IL-1 family (IL-1?, IL-1?, and IL-1 receptor antagonist) are involved in the pathogenesis of HCC. MATERIAL AND METHODS This study aimed to determine whether polymorphisms in the IL-1 family of genes are associated with HCC. We analyzed 178 HCC patients and 397 controls to investigate the association between polymorphisms in IL-1?, IL-1?, and IL-1 receptor antagonist (IL-1RA) genes and HCC in the Korean population. All subjects were genotyped for the selected SNPs in IL-1?, IL-1?, and IL-1RA genes by Golden-Gate SNP Genotyping Assay. RESULTS Statistical analysis revealed a significant association at IL-1? between HCC and controls. Three individual polymorphisms (rs1143633, rs3917356, and rs1143627) were found to be associated with HCC. The SNPs of IL-1b gene (rs1143633A>G and rs1143627T>C) protected against HCC in the dominant model (p=0.027, OR=0.59, 95% CI=0.37-0.94; p=0.019, OR=0.56, 95% CI=0.34-0.91). The SNP of IL-1? gene (rs3917356G>A) increased the risk of HCC in the recessive model (p<0.001, OR=2.58, 95% CI=1.53-4.33), whereas other SNPs in IL-1? and IL-1RA showed no significant association between HCC patients and controls. CONCLUSIONS These results suggest that IL-1? in the IL-1 family contributes to HCC susceptibility.
| S-EPMC5996846 | biostudies-literature
Project description:IntroductionThe development and progression of hepatocellular carcinoma (HCC) is a multistage process involving the deregulation of genes that are crucial to cellular processes. Multiple risk factors are correlated with HCC. MicroRNA is differentially expressed in the development of different types of malignancies, including hepatic malignancy. Single nucleotide polymorphisms (SNPs) are the most common sequence variation in the human genome. SNPs in miRNAs may affect transcription, processing, or target recognition and result in malignant disease. The aim of the study was to determine the association between microRNA gene polymorphisms and the development of HCC in Egyptian patients.Material and methodsThis study included 200 individuals who were matched in age and sex. Tumour staging was done using the BCLC staging system. Quantification and genotyping of microRNA were performed.ResultsAmong the 200 patients, 2 groups were described: group I included 90 HCC patients with a male majority (72.2%), and group II comprised 110 controls. Three microRNA SNPs were assayed in both patients and controls. There was a significant association between rs10061133 miR-499b and the risk of HCC. The genotypes GG or G allele were significantly associated with an increased risk of HCC (GG: OR = 2.91, 95% CI: 1.23-4.22, p = 0.013; G allele: OR = 1.79, 95% CI: 1.12-2.15, p = 0.026) compared with the genotype of AA or AG or A allele.ConclusionsThere is an association between the miRNA SNPs and the susceptibility to HCC, to explore some roles and mechanisms of SNPs within miRNAs in the occurrence and development of HCC.
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Project description:AimTo 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.MethodsHepatocellular 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 investigated five TNF-α polymorphisms, which are TNF-α -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A. The TNF-α genotype frequencies, genotype combinations and haplotypes were analyzed to disclose the association with HCC.ResultsNone of the TNF-α polymorphisms was significantly associated with HCC. However, nine genotype combinations had associations with increased likelihood of HCC. Among them, TNF-α -1031/-857/-238 TT/CC/GA (AOR = 18.849, 95%CI: 2.203-161.246, P = 0.007), TNF-α -1031/-308/-238 TT/GG/GA (AOR = 26.956, 95%CI: 3.071-236.584, P = 0.003), and TNF-α -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-α polymorphisms which were significantly associated with HCC. They are TNF-α -1031/-863/-857/-308/-238 T-C-C-G-A (OR = 25.824, 95%CI: 1.491-447.223, P = 0.0005), TNF-α -1031/-857/-308/-238 T-C-G-A (OR = 12.059, 95%CI: 2.747-52.950, P < 0.0001), TNF-α -1031/-857/-238 T-C-A (OR = 10.696, 95%CI: 2.428-47.110, P = 0.0001), TNF-α -1031/-308/-238 T-G-A (OR = 7.556, 95%CI: 2.173-26.280, P = 0.0002) and TNF-α -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-α -1031 CC genotype had better survival than those with the TT genotype (AOR = 5.795, 95%CI: 1.145-29.323).ConclusionAlthough no single TNF-α polymorphism is associated with HCC in this study, some TNF-α genotype combinations and haplotypes are associated with HCC. In addition, HCC Okuda stage III cases with the TNF-α -1031 TT genotype may have a better prognosis than those with the CC genotype.
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Project description:TARGET:Our study was to investigate the effects of interleukin-6 (IL-6) polymorphisms (rs2069837 and rs17147230) on the risk for hepatocellular carcinoma (HCC). METHODS:A total of 226 HCC cases and 220 healthy controls were admitted into the study and genomic DNA was extracted from the peripheral blood. The genotyping was conducted by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the relationship of IL-6 rs2069837 and rs17147230 polymorphisms with HCC susceptibility. RESULTS:The frequency of GG genotype of rs2069837 was higher in HCC patients, compared with controls (P < 0.05). Moreover, the results indicated that GG genotype was related with increased risk for HCC (OR = 2.303, 95% CI = 1.056-5.025). Similarly, the risk for G allele carriers was higher than that of A allele (OR = 1.392, 95% CI = 1.046-1.852). For rs17147230, TT genotype showed strong effect on HCC susceptibility (OR = 2.089, 95% CI = 1.135-3.845) and T allele appeared to be a risk factor for HCC (OR = 1.326, 95% CI = 1.010-1.740). Further analysis showed that G-T haplotype was associated with increased risk for HCC (OR = 3.125, 95% CI = 1.845-5.294, P = 0.000). CONCLUSION:IL-6 rs2069837 as well as rs17147230 were associated with HCC susceptibility. In addition, G-T haplotype also served as a genetic-susceptibility factor for HCC.
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Project description:BackgroundInterleukin-18 (IL-18) and interferon-γ (IFN-γ) are cytokines of crucial role in inflammation and immune reactions. There is a growing evidence supporting important roles for IL-18 and IFN γ in tuberculosis (TB) infection and anti-tuberculosis immunity.ObjectiveTo evaluate the role of polymorphisms in IL-18-607 and -137 and INF-γ +874 in susceptibility to TB infection among Egyptian patients.MethodsA case control study was conducted to investigate the polymorphism at IL-18-607, -137 and INF-γ+874 by sequence specific primer-polymerase chain reaction (SSP- PCR) in 105 patients with pulmonary and extra pulmonary tuberculosis and 106 controls.ResultsA significant protective effect against TB was found in homozygous CC genotype at IL-18 -137G/C, in addition to a 7-fold risk with GG and GC genotypes in the recessive model. Apart from a decreased risk with the AC genotype, no association was detected between the susceptibility to TB and different genotypes or alleles at the IL-18 -607A/C site. The homozygous AA genotype in INF-γ+874 showed a significant higher risk to TB than the homozygous TT or heterozygous AT genotypes with nearly a 2-fold risk of TB infection with the A allele. Regarding haplotype association, the GC haplotype was strongly associated with TB infection compared to other haplotypes.ConclusionThese findings suggest; for the first time in Egypt; a significant risk to TB infection with SNP at the IL-18-137G/C with no LD with SNP at the IL-18-607 site. The homozygous AA genotype in INF-γ+874 showed a significant higher risk to TB than the homozygous TT or heterozygous AT genotypes.
| S-EPMC7790531 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is a common cancer with substantial cancer-related deaths worldwide. Deregulation of some genetic polymorphisms has been identified in HCC.ObjectiveWe aimed to demonstrate the frequency of miRNA 196a2 rs11614913 and miRNA 34 b/c rs4938723 gene polymorphisms in HCC patients and their correlation with the clinical features and laboratory findings at diagnosis.Subjects and methodsThe study was performed on 40 patients with newly diagnosed HCC and 40 patients with liver cirrhosis in addition to 40 age and sex-matched healthy controls. Detection of miRNA 196a2 rs11614913 and miRNA 34 b/c rs4938723 gene polymorphisms was determined by PCR-RFLP.ResultsHCC patients had significantly higher frequency of miR-196-2a rs11614913 CC genotype when compared with cirrhotic patients (60.0 % versus 30.0 %, p=0.013). In spite of the fact that HCC patients also had higher frequency of miR-196-2a rs11614913 CC genotype in comparison to controls, the difference fell short of statistical significance (60.0 % versus 42.5 %, p=0.18). No significant differences were found between the studied groups regarding the frequency of miR-196-2a alleles. miR34 b/c rs4938723 CC genotype was the only identified genotype in all participants in the three studied groups. No significant associations were found between the different clinical and laboratory variables and genotypic variations in HCC patients.ConclusionsThis study identified miR-196a2 rs11614913 CC genotype as a risk factor for HCC development while we failed to document similar relation for miR-34b/c rs4938723 polymorphism.
| S-EPMC9375611 | biostudies-literature
Project description:Aim of the studyWe reported the association between interleukin 6 polymorphisms (rs1800796, rs1800795, rs2069837, rs17147230, and rs1800797) and hepatocellular carcinoma (HCC) susceptibility in a meta-analysis.Material and methodsThe studies were retrieved by searching the search terms in Scopus, PubMed, Web of Science, and Cochrane Library databases until June 2020. The analyses were done by RevMan 5.3 software using odds ratios (ORs) and 95% confidence intervals (CIs) and the analysis of publication bias and sensitivity analyses were performed by CMA 2.0 software.ResultsSearching through the databases, 316 records were retrieved and finally 13 studies were analyzed in the present meta-analysis. For the rs1800797 polymorphism, there was an elevated risk of AA genotype (OR = 2.68, p = 0.03) in HCC patients compared to healthy controls. Also, there was an elevated risk of AA (OR = 3.06, p = 0.04) and GA (OR = 2.61, p = 0.005) genotypes in HCC patients compared to liver cirrhosis patients. For rs2069837 polymorphism, there was an elevated risk of GG genotype (OR = 2.25, p = 0.01) in HCC patients compared to healthy controls. For rs17147230, T allele (OR = 1.31, p = 0.03) and TT genotype (OR = 1.83, p = 0.02) had elevated risks in HCC patients compared to healthy controls.ConclusionsThe present meta-analysis confirmed that there was an elevated risk of the AA and GA genotypes of rs1800797 polymorphism and the GG genotype of rs2069837, and the T allele and TT genotype of rs17147230 in HCC.
| S-EPMC7816640 | biostudies-literature
Project description:PurposeTo test the involvement between IL-18 and IL-6 genetic polymorphisms and susceptibility to Type 1 diabetes (T1D).MethodsSingle nucleotide polymorphisms (SNPs) at positions -607A/C and - 137G/C in IL-18 promoter region were examined by sequence specific primers-polymerase chain reaction (SSP-PCR) and position -174G/C in promoter region of IL-6 gene which analyzed by Mutagenically Separated PCR (MS-PCR) in 104 T1D participants and 114 controls.ResultsIL-18 -137GC and -137CC genotypes and -137C allele were significantly decreased in T1D subjects (P < 0.05), while -137GG genotype was insignificantly increased as compared to controls. A significant decrease was detected in haplotype -137C/-607C frequency in T1D participants compared with controls (OR = 0.04, P < 0.001). There was significant association between IL-18 -607 of (CC, AC and AA genotypes) in age at diagnosis, glycated hemoglobin (HbA1c) and higher body mass index (BMI) (P < 0.05).ConclusionThis study demonstrated that IL-18 gene promoter polymorphisms might be associated with susceptibility to T1D in Egyptian children. Individuals carrying CC genotype at position -137 of IL-18 promoter may be at a low risk of T1D progression. Additionally, the susceptible combination of IL-18 and IL-6 cytokine genes associated with T1D highlight their risk toward the disease.Supplementary informationThe online version contains supplementary material available at 10.1007/s40200-021-00763-w.
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