This study aimed to quantify the extent to which IGF-1 mediates the association between BMI and liver cancer risk, clarifying its role in adiposity-related liver carcinogenesis. A prospective analysis was conducted using data from 432,203 UK Biobank participants, using four liver cancer definitions: ICD-10 C22 and C220, each excluding diagnoses within 24 or 60 months post-baseline. Linear regression assessed the BMI-IGF-1 relationship. Cox proportional hazards models and restricted cubic spline analyses examined associations between BMI, IGF-1, and liver cancer risk, with adjustments for covariates. Mediation analysis with 5000 bootstrap iterations evaluated IGF-1's mediating effect. Elevated BMI was positively correlated with liver cancer risk (multivariable HR = 1.071; p < 0.0001). This association attenuated after adjusting for IGF-1 (HR = 1.037; p < 0.0001). BMI negatively correlated with IGF-1 (multivariable β = −0.150; p < 0.0001). IGF-1 showed a non-linear relationship with liver cancer risk, with lower levels (approximately less than 18 nmol/L) linked to higher risk. IGF-1 mediated 37.76%–53.64% of the BMI-liver cancer association. IGF-1 substantially mediates the association between BMI and liver cancer risk, suggesting BMI-related IGF-1 reduction is a potential mechanistic pathway. • Elevated BMI is positively associated with an increased risk of liver cancer, and this association is attenuated after adjusting for IGF-1. • BMI shows a significant negative correlation with IGF-1 levels, and IGF-1 has a non-linear relationship with liver cancer risk, with lower levels (below ~18 nmol/L) linked to higher risk. • IGF-1 substantially mediates 37.76%–53.64% of the association between BMI and liver cancer risk, indicating BMI-related IGF-1 reduction as a potential mechanistic pathway.
Yang et al. (Sun,) studied this question.