Polymorphisms of interferon gamma gene and risk of hepatocellular carcinoma in Korean patients with chronic hepatitis B viral infection

Backgrounds/Aims: Increasing evidence supports the contribution of the pro-/anti-inflammatory cytokine balance and genetic factors to hepatocellular carcinoma (HCC). Here, we investigated whether genetic interferon gamma polymorphisms were associated with HCC in Korean patients with chronic hepatitis B. Methodology: We genotyped a single nucleotide polymorphism (SNP, rs2430561, +874A/T) and a microsatellite (rs3138557, (CA) repeat), located in the first intron of the interferon gamma gene, by direct sequencing and the gene scan method. A population-based case-control study of HCC was conducted and included 170 patients with chronic hepatitis and HCC, and 171 with chronic hepatitis B patients without hepatocellular carcinoma in a Korean population. Results: Genotype and allele distributions of the interferon gamma gene SNP were associated with HCC. The frequencies of the AA genotype and the A allele were significantly increased in hepatocellular carcinoma subjects (p<0.05). Combined analysis using the genotype of rs2430561 and the number of microsatellites revealed that the frequencies of AT-CA₁₂ and TT-CA₁₂ increased significantly in hepatocellular carcinoma subjects (p<0.0001). Conclusions: Our results suggest that the interferon gamma gene may be a susceptibility gene and a risk factor for HCC in the Korean population.