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.
Highlights
The majority of HCC cases occur in patients with cirrhosis or with chronic liver diseases resulting in the release of inflammatory mediators causing cell injury followed by regeneration mediated by the immune response which plays a major role in hepatocarcinogenesis (Choi and Lim., 2017)
PCR with sequence-specific primers was used to detect the Single nucleotide polymorphisms (SNPs) of tumor necrosis factor-α (TNF-α) gene -238G>A and IL-18 gene -607 C>A in all the studied subjects
On performing odds ratio on the different genotype subgroups of IL18 gene SNP-607C>A, it was found that individuals harboring the AA genotype were 5 folds riskier to develop HCC compared to those carrying the CC/CA genotypes (OR: 5) (Table 2)
Summary
The majority of HCC cases occur in patients with cirrhosis or with chronic liver diseases resulting in the release of inflammatory mediators causing cell injury followed by regeneration mediated by the immune response which plays a major role in hepatocarcinogenesis (Choi and Lim., 2017). TNFα-238G>A polymorphism has been reported to alter the risk of several types of cancers, such as HCC, breast cancer, lung cancer, non-Hodgkin lymphomas, and prostate cancer (Ma et al, 2014).Interleukin-18 (IL-18) belongs to the IL-1 cytokine superfamily and it is a novel proinflammatory cytokine. It was initially recognized as an interferon-γ (IFN-γ)-inducing factor and has a wide range of functions, including induction of the synthesis of IFN-γ in T cells and natural killer cells through synergistic action with IL-12 and IL-10, respectively, promotion of Th1-type immune responses, and enhancement of the proliferative response and cytokine production of activated T cells (Zhang et al, 2016). Several SNPs in the promoter region and two polymorphisms in the 5′-nontranslated region of IL-18 have been identified, among these, the functional polymorphism in the promoter region at loci −607C>A the most studied (Jia et al, 2016)
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