article · Egyptian Liver Journal
Abstract Background Hepatocellular carcinoma (HCC) remains a major global health burden, particularly among individuals with chronic hepatitis C virus (HCV) infection. Genetic factors, including single-nucleotide polymorphisms (SNPs), play an important role in susceptibility to HCC and its progression. This study aimed to investigate the association of MICA (rs2596542) and COMT (rs4680) polymorphisms with HCC risk in Egyptian patients infected with HCV. Methods A case-control study was conducted with 200 participants, including 100 HCC patients infected with HCV and 100 healthy controls. Genotyping of MICA and COMT polymorphisms was performed using real-time PCR. Clinical and biochemical parameters, such as AFP, ALT, AST, and albumin levels, were assessed. Statistical analyses were carried out to investigate genotype distributions and their association with the risk of HCC. Results The MICA TT genotype was significantly more prevalent in HCC patients compared to controls (35.0% vs. 11.0%, p < 0.0001), indicating a significant association with increased HCC risk. In contrast, the COMT AA genotype was more prevalent in controls (62.0% vs. 40.0%, p = 0.007), suggesting a potential protective effect. Analysis of genotype distribution across HCC histological grades showed no statistically significant differences for either MICA or COMT polymorphisms (all p > 0.05), although non-significant trends toward higher frequencies of mutant genotypes in advanced grades were observed. Increased levels of AFP and liver enzymes were associated with advanced grades of HCC. Multivariate analysis revealed that AST, independent of genetic variants, is a significant risk factor (OR = 4.46, p = 0.005), while higher albumin levels were protective (OR = 0.31, p = 0.012). Conclusions This study suggests that the MICA rs2596542 polymorphism is significantly associated with susceptibility to HCC, while the COMT rs4680 may have a modest role. However, neither polymorphism showed a significant association with histological grade. The integration of genetic variants with clinical biomarkers may improve risk stratification in HCC. Further large-scale studies are warranted to validate these findings.
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DOI: 10.1186/s43066-026-00523-6
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