Sex-specific disparities in alcohol-associated liver disease and cancers

Alcohol consumption is a known risk factor for liver disease and cancers; however, sex-specific susceptibilities and biological mechanisms linking various dimensions of alcohol intake to alcohol- associated liver disease (ALD) and cancers remain poorly understood.
Researchers analysed 365,966 participants from the UK Biobank to evaluate hazard ratios (HRs) for alcohol dose, frequency, and pattern in relation to ALD and alcohol-related cancers. In a representative subcohort (n = 38, 328), plasma proteomic profiling (2911 proteins) was conducted to identify sex-specific biological drivers.
Over a median 13. 8- year follow- up, every 70 g/week increment in alcohol intake was associated with a disproportionately higher risk of ALD in females (HR = 1. 21, 95% CI: 1. 19-1. 23) than in males (HR = 1. 06, 95% CI: 1. 06-1. 06). At 200 g/week, females had a 2. 8- fold higher risk of ALD than males. Females also showed greater vulnerability to oesophageal cancer at higher intake levels. Daily drinking and drinking without meals significantly amplified risks across both sexes. Researchers identified carcinoembryonic antigen- related cell adhesion molecule 16 (CEACAM 16) as the strongest shared biological link between alcohol consumption and alcohol-related liver disease (ALD) in both men and women. This protein appeared to account for a meaningful proportion of the relationship between alcohol use and liver disease.
The study also found important differences between the sexes. In men, alcohol-related biological changes were mainly linked to inflammatory pathways, suggesting that excessive immune activity may play a key role in liver damage. In women, the main pathways were related to maintaining healthy cells and tissue structure, indicating that alcohol may affect liver health through different biological mechanisms.
This study provides epidemiological and proteomic evidence that sex significantly modifies alcohol- induced health risks, warranting the implementation of sex- stratified guidelines and clinical screening for alcohol- associated diseases.
Source: Fang, L., Zhao, J., Liu, G., Shi, Y., Zeng, H., Ding, Z., et al. (2026) Sex-specific disparities in alcohol-associated liver disease and cancers: Insights from a large, prospective cohort and plasma proteomics. Cancer Epidemiology, 103,103129. https://doi.org/10.1016/j.canep.2026.103129