Serum Soluble Fas Levels and Incidence of Liver Cancer in Nested Case–Control Study

Abstract Background: Soluble Fas (sFas) plays various roles in carcinogenesis and tumor dissemination by preventing apoptosis via binding to Fas ligand. We analyzed associations of serum sFas levels with the incidence of liver cancer in a prospective case–control study nested in the Japan Collaborative Cohort Study. Methods: A baseline survey was conducted from 1988, with blood samples obtained from 39,242 subjects. Patients diagnosed with liver cancer were regarded as cases. Two or three controls were selected and matched for sex, age, and geographic area. Conditional logistic regression was used to estimate ORs for cancer incidence associated with sFas. Results: This study contained 86 cases and 249 controls. After controlling for alcohol intake, body mass index, smoking, and hepatitis viral infection, participants with high sFas showed elevated risk of cancer (Ptrend = 0.003) and the third tertile of sFas showed a higher risk compared with the first tertile [OR, 3.53; 95% confidence interval (CI), 1.28–9.69]. In hepatocellular carcinoma, high sFas was associated with elevated risk (Ptrend < 0.001). In men and the elderly, subjects in the highest tertiles showed higher cancer risk. Limiting subjects to those followed for 3 years, high sFas was related to liver cancer risk (Ptrend = 0.033) and the third tertile showed a higher risk compared with the first (OR, 2.94; 95% CI, 0.94–9.14). Conclusions: High serum sFas may be related to future risk of liver cancer. Impact: Our findings highlight this biomarker for further analysis in pooled investigations with different/larger prospective cohorts.