Genetic polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 promoter may not be associated with development of hepatocellular carcinoma

Abstract

This study meta-analyzed the literature on possible association of polymorphisms -137 (rs187238) and -607 (rs1946518) in the interleukin-18 (IL-18) promoter with risk of hepatocellular carcinoma (HCC). The analysis included 8 case-control studies on the -137 polymorphism (1,318 cases, 2,254 controls) and 7 case-control studies on the -607 polymorphism (1,262 cases, 1,696 controls). None of the five genetic models suggested a significant association between the -137 polymorphism and HCC risk: allelic model, OR 0.99, 95% CI 0.74–1.34, P = 0.97; recessive model, OR 0.98, 95% CI 0.65–1.46, P = 0.91; dominant model, OR 1.35, 95% CI 0.73–2.52, P = 0.34; homozygous model, OR 0.99, 95% CI 0.65–1.49, P = 0.95; heterozygous model, OR 0.99, 95% CI 0.66–1.48, P = 0.94. Similar results were obtained in subgroup analyses of Asian patients, Chinese patients, or patients with hepatitis B virus (HBV)-related HCC. Similar results were also obtained for the -607 polymorphism across the entire study population as well as in the three subgroups. The available evidence suggests no significant association of the -137 or -607 polymorphisms with risk of HCC in general or specifically of HBV-related HCC. These conclusions should be verified in large, well-designed studies.

Association of genetic variants in the interleukin‐18 gene promoter with risk of hepatocellular carcinoma and metastasis in patients with hepatitis C virus infection

“…Zhang et al i ndicated that the HBV‐related HCC group exhibited significantly higher frequencies of AA genotype and A allele of the IL‐18 (‐607C/A) SNP than the healthy subjects, but the genotypic distributions and allelic frequencies of the HBV‐related HCC group and the chronic HBV infection group were similar. In contrast to our results, previous studies performed by Bao et al , Lau et al , and Zhu et al exhibited no significant relationship between this SNP and the risk of HCC in various populations.…”

“…Similar to our findings, Teixeira et al found that the frequencies of genotypes IL‐18‐137CC, GC, and GG did not differ significantly in patients with or without metastasis. On contrary to our findings, Zhu et al in a meta‐analysis proposed that the IL‐18 (‐137G/C) SNP may be useful for predicting metastasis or recurrence.…”

“…On the contrary, Karra et al and Lau et al demonstrated that this polymorphism was associated with a higher risk of developing HBV‐related HCC. Moreover, Teixeira et al , Zhu et al , and Zhang et al observed that the IL‐18 (‐137G/C) SNP was not associated with HCC risk in HBV‐infected patients.…”

“…Epidemiological studies revealed that a combination of environmental factors, along with genetic factors play a pivotal role in hepato‐carcinogenesis . Hepatitis C virus (HCV) has been estimated to infect 170 million patients worldwide, with a high incidence rate among Egyptians (14–18%) .…”

Inflammasomes and their roles in the pathogenesis of viral hepatitis and their related complications: An updated systematic review

“…The protective roles played by the -137C allele against the chronic form of hepatitis B and HCC related complications have also been confirmed by investigators [97,98]. However, Zhu et al, revealed that the IL-18 -137 G/C polymorphism is not associated with the risks of HCC complication of hepatitis B [99]. Associations of other polymorphisms of IL-18 gene have also been reported by previous studies [100,101].…”