AbstractBackground & Aims Sex-specific associations between adiposity and death of primary liver cancer (PLC) remain poorly characterized, particularly those related to emerging anthropometric indices and populations with high abdominal adiposity. Methods 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. Results After a median follow-up time of 22.0 years for women and 16.1 years for men, 300 women and 485 men died of 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 to 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 body mass index (BMI) best predicted PLC death in both sexes, highlighting the need for sex-specific adiposity management. Conclusions Sex-specific differences exist in the association between adiposity and PLC death. The non-linear pattern observed in men warrants mechanistic investigation for potential hormonal or metabolic mediators of the adiposity-PLC death relationship. Impact and implications 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) 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 critical modifiable risk factor for primary liver cancer, urging policymakers to adopt sex-specific adiposity strategies, encourage healthcare professionals and researchers to investigate the underlying mechanisms of the observed non-linear associations in men, and utilize the superior predictive power of combined models like CUN-BAE and BMI to identify high-risk individuals.
Yang et al. (Sun,) studied this question.