Transforming Growth Factor-β1 as a Predictor for the Development of Hepatocellular Carcinoma: A Nested Case–Controlled Study

BACKGROUND Transforming growth factor-β1 (TGF-β1) reportedly acts as a tumor suppressor in tumorigenesis. However, little is known as to how TGF-β1 concentrations change prior to the development of hepatocellular carcinoma (HCC) in humans. We examined the association between the serum TGF-β1 concentrations and death from HCC to determine whether the serum TGF-β1 can be a predictor of incident HCC. METHODS We conducted a nested case-controlled study of participants in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. We used a conditional logistic regression analysis to estimate the adjusted relative risks (aRRs) of death from HCC according to the serum TGF-β1 concentrations among 1940 participants including 83 patients with HCC and 1857 controls matched for age, sex, and hepatitis C virus (HCV)-antibody seropositivity. FINDINGS When serum TGF-β1 was modelled as a continuous variable, the aRR of death from HCC associated with a decrement of 7.9ng/mL (one standard deviation) in the serum TGF-β1 concentrations was 2.3 (95% CI 1.7-3.0, P<0.001) for all the subjects. The area under the receiver operating characteristic curve for the serum TGF-β1 concentrations was 0.78 (P<0.05). INTERPRETATION Our finding suggests that TGF-β1 serves as a predictor for HCC.