Fas/FasL polymorphisms are associated with hepatitis C related cirrhosis and serum Alpha-Fetoprotein with hepatocellular carcinoma patients

Background: Host genetic factors that may confer a susceptibility to chronic hepatitis and the progression of hepatocellular carcinoma (HCC) are largely unknown. Apoptosis is an important fail-safe check for the hepatitis virus and HCC development, in which Fas/FasL hepatocyte expression contributes substantially. Aim: To determine whether the Fas/FasL gene promoter polymorphism at Fas-670, Fas-1377 and Fas-L844 are associated with the risk of virus hepatitis or the prognosis of HCC patients. Patients and methods: We conducted a retrospective hospital-based case–control study in which 142 HCC patients were enrolled. The study patients were divided into three groups: 1) hepatitis B with Lamivudine treatment (N = 107), 2) hepatitis C with interferon treatment (N = 50), and 3) a non-HCC control group of patients (N = 300). Of the 142 total enrolled patients from the first two groups, 110 underwent liver resection. There were 59 patients with early recurrence (<1 year post operation), 31 patients with late stage HCC (CLIP score 2–6), and 22 patients with AFP >400 ng/ml. All of the patients in these groups were tested for Fas/FasL polymorphism by PCR-RFLP. The frequency of allele and genotype were compared between each group. The significant SNP (single nucleotide polymorphism) correlated with patient clinical characteristics and was a surrogate for recurrence or survival analysis. Results: In the control group, the C/T ratio in FasL was 71.4/28.6, the A/G ratio in Fas670 was 55.28/44.7, and the A/G ratio in Fas1377 was 41.3/58.7. There were no significant differences between these numbers and similar numbers in the HCC, HBV, HCV or surgical group. In the genotype pattern of Fas670, the A/A to A/G + G/G ratio was 30.3/69.7 and they are significant to the HCV hepatitis group 16.0/84.0 (the P value = 0.026). In Fas1377, the A/A + A/G to G/G ratio was 66.7/33.3 and they are significant to the HCV hepatitis group 84.0/16.0 (p < 0.01). Comparing the surgical HCC group of early stage (CLIP score 0–1) and late stage HCC (CLIP score 2–6), C/C to T/C + T/T ratios are significant (p < 0.01) in the genotype of FasL. Comparing the surgical HCC group of AFP <400 ng/ml and >400 ng/ml, C/C to T/C + T/T ratios are significant (p < 0.01) in the genotype of FasL. There was no difference in the overall 10-year survival or recurrence rate between FasL genotype C/C and T/C + T/T. Conclusions: The apoptosis mechanism of Fas/FasL interaction may contribute to HCV-related hepatitis and the late stage (CLIP score 2–6) of the surgical HCC group. The genetic polymorphisms of Fas1377 could play a role in the process of hepatitis C virus infection transforming to liver cirrhosis. Additionally, our research suggests that there may be a correlation between the genetic polymorphisms of FasL in HCC patients, and patient prognosis based upon serum AFP levels