Serum soluble Fas levels and incidence of biliary tract cancer in a nested case-control study

Abstract

Abstract Background: Soluble Fas (sFas) plays multiple roles in tumorigenesis and cancer dissemination by avoiding apoptosis via connection to Fas ligand. We assessed associations of serum sFas levels with the incidence of extrahepatic biliary tract cancer (eBTC) in a prospective case-control study nested in the Japan Collaborative Cohort study. Methods: A baseline survey was conducted from 1988 using blood samples from 39,242 individuals (35% of 110,585). Patients diagnosed with eBTC, before the end of 1997, were regarded as cases. Odds ratios (ORs) for cancer incidence associated with sFas were estimated by conditional logistic regression. Results: This study included 73 cases and 215 controls. Participants with high sFas showed an elevated risk of cancer (P-trend = 0.01) and the third tertile of sFas showed a higher risk compared to the first tertile (OR 3.27, 95% confidence interval [CI] 1.37–7.80). In both gallbladder and extrahepatic bile duct cancers (n = 33 and 40, respectively), high sFas was associated with elevated risk (P-trend = 0.04 and 0.02, respectively). In women and the non-elderly, subjects in the highest tertiles showed higher cancer risk. Limiting subjects to those followed for over 2 years, high sFas was related to cancer risk (P-trend = 0.02) and the third tertile showed a higher risk compared to the first (OR 3.03, 95%CI 1.14–8.07). Conclusions: High serum sFas may be related to future risk of eBTC. Impact: These findings highlight the need for additional studies of this biomarker in large prospective cohorts and through integrated analysis involving other cohorts.