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

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver, characterized by high vascularization and rapid tumor progression. The current case-control study aimed to analyze the influence of -607C/A and -137G/C polymorphisms in the interleukin-18 (IL-18) promoter on the risk of HCC occurrence and metastasis in Egyptian patients infected with hepatitis C virus (HCV). Both genetic variations were genotyped in 279 subjects including HCV patients with and without HCC and unrelated healthy subjects, using the allele-specific polymerase chain reaction (AS-PCR) method. The relationship between clinico-laboratory parameters including serum level of alpha-fetoprotein (AFP) and these polymorphisms was evaluated in HCC patients. The IL-18-607A allele and AA genotype were significantly related to a higher risk of developing HCC when comparing patients with HCC and controls, and were significantly related to a higher risk of metastasis when comparing metastatic and nonmetastatic groups in the Egyptian patients. In contrast, the IL18-137C allele and GC genotype were significantly related to a lower risk of developing HCC when comparing patients with HCC and controls, and HCV patients with and without HCC. A significant association was found between multinodular HCC and IL-18-607AA genotype, while, uninodular HCC was significantly associated with IL-18-137GG genotype. In addition, IL18-607AA and -137GG genotypes showed significant association with higher level of serum AFP. The detection of polymorphisms in the IL-18 promoter, in a combination with an evaluation of level of serum AFP, could be used as a molecular biomarker in the early diagnosis of HCC, which would aid the early management of the disease, thus decreasing the rate of mortality of this disease. © 2018 IUBMB Life, 70(2):165-174, 2018.