Large cohort studies assessing sex-specific associations between anthropometric indices and liver cancer death

Sex-specific associations between adiposity and death from primary liver cancer (PLC) remain poorly characterized, particularly those related to emerging anthropometric indices and populations with high abdominal adiposity.

In two prospective cohort studies, the sex-specific associations between 16 anthropometric indices (six traditional, 10 emerging) and PLC death were examined in 72,691 women and 59,892 men in China. Cox proportional hazards regression models with restricted cubic spline functions were applied to evaluate the associations between adiposity indices and PLC death.

After a median follow-up time of 22.0 years for women and 16.1 years for men, 300 women and 485 men died from PLC. We observed distinct risk patterns: women demonstrated positive linear associations for 11 indices (five traditional, six emerging) with PLC death, with highest-quartile individuals showing a 46-82% elevated death risk compared with lowest-quartile counterparts, especially in premenopausal women. Conversely, men displayed U-shaped associations for 10 indices, indicating that death risk was minimized at moderate adiposity levels. Notably, the combined model of the Clínica Universitaria de Navarra Body Adiposity Estimator (CUN-BAE) and BMI best predicted PLC death in both sexes, highlighting the need for sex-specific adiposity management.

Sex-specific differences exist in the association between adiposity and PLC death. The nonlinear pattern observed in men warrants mechanistic investigation for potential hormonal or metabolic mediators of the adiposity-PLC death relationship.

This study represents the first comprehensive investigation into the sex-specific associations between 16 anthropometric indices (traditional/emerging) and liver cancer death in two Chinese cohorts. Findings show distinct patterns: positive linear in women (especially premenopausal women) and U-shaped associations in men, with the lowest death risk observed at moderate adiposity levels. Models incorporating CUN-BAE and BMI improved prediction for liver cancer death in both sexes. These findings highlight adiposity as a crucial modifiable risk factor for PLC, urging policymakers to adopt sex-specific adiposity strategies, encouraging healthcare professionals and researchers to investigate the underlying mechanisms of the observed nonlinear associations in men, and utilizing the superior predictive power of combined models, such as CUN-BAE and BMI, to identify high-risk individuals.