Association between MICA rs2596542 and MTHFR rs1801133 Polymorphisms with the Risk of Hepatocellular Carcinoma

Abstract

Background: Hepatocellular carcinoma (HCC) susceptibility is influenced by various risk factors, including viral infections, alcohol consumption, tobacco use, and genetic predisposition. The MICA rs2596542 and MTHFR rs1801133 gene polymorphisms have been implicated in HCC pathophysiology.

Objective: This study aims to evaluate the association between single-nucleotide polymorphisms in MICA rs2596542 and MTHFR rs1801133 and the risk of HCC development.

Methods: A total of 240 participants were enrolled, including 80 individuals with HCC associated with hepatitis C virus (HCV) in Group I, 80 individuals with HCC linked to hepatitis B virus (HBV) in Group II, and 80 age- and gender-matched healthy controls in Group III. Genetic polymorphisms of MICA rs2596542 and MTHFR rs1801133 were identified using real-time polymerase chain reaction analysis. This study is distinct in analyzing these SNPs in a well characterized Egyptian cohort with explicit virus stratified comparisons (HBV vs HCV) and combined genotype–clinical modeling to evaluate both susceptibility and clinical correlates.

Results: A significant increase in the heterozygous CT genotype of MICA rs2596542 and in the T allele frequency was observed in Group II (HCC/HBV) compared to Group III (controls). The MICA CT genotype (rs2596542) was clinically associated with HCC stage and alpha-fetoprotein (AFP) levels. Similarly, the AA and GA genotypes of MTHFR rs1801133 and their mutant A allele frequency were notably elevated in Groups I and II compared to controls. The GA and AA genotypes of MTHFR rs1801133 showed clinical correlations with HCC staging and AFP levels. Multivariate analysis identified hypercalcemia, back pain, metastatic disease, and multiple lesions as independent predictors of survival.

Conclusion: MICA (rs2596542) and MTHFR (rs1801133) polymorphisms were determined to be independent risk factors for HCC disease susceptibility. Notably, they were significantly associated with HCC development. These results indicate that MICA (rs2596542) and MTHFR (rs1801133) could represent valuable markers to recognize individuals who are at a greater probability of developing HCC. The most independent factors affecting survival were hypercalcemia, back pain, metastatic disease, and the occurrence of more than one lesion when multivariate analysis was performed.