Insulin-Like Growth Factor 2 and Incidence of Liver Cancer in a Nested Case-Control Study.

Background: Insulin-like growth factor (IGF)2 is a potent mitogen. To elucidate the relationship between IGF2 and risk of tumorigenesis, we analyzed associations between serum levels of IGF2 and 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 using blood samples from 39,242 subjects. Those who had been diagnosed with liver cancer by 1997 were regarded as cases. For each case, we randomly selected 2 or 3 controls matched for sex, age, and residential area. Conditional logistic regression was used to estimate odds ratios (ORs) for cancer incidence associated with IGF2. Results: This analysis included 86 cases and 294 controls. Low IGF2 was associated with risk of future liver cancer (P-trend <0.001). After controlling for alcohol intake, body mass index, smoking, hepatitis viral infection, IGF1, and IGF-binding protein-3, participants with low IGF2 displayed a higher risk of liver cancer (P-trend <0.001). Individuals in quintiles 2-5 showed lower risk compared to quintile 1 (OR range, 0.05-0.16). In both sexes and in both non-elderly and elderly groups, subjects in the lowest quintiles showed higher risks of liver cancer. Limiting subjects to those followed for 3 years, low IGF2 was associated with cancer risk (P-trend <0.001). Conclusions: Our findings suggest that low serum IGF2 level, especially below 460 ng/mL, is related to future risk of liver cancer. Impact: Our findings highlight this important biomarker for further analysis in large prospective cohorts and pooled investigation with other cohorts.