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Association Between Allostatic Load, Genetic Susceptibility, and Liver Cancer Incidence: A Large-Scale Prospective
Danling Li1, Zhongming Zhou1, Ganbo Liang1
1Department of Thyroid, Breast and Hernia Surgery, General Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, People's Republic of China.
International Journal of Cancer
|July 17, 2026
Summary
Chronic stress, measured by allostatic load (AL), significantly increases primary liver cancer (PLC) risk. Lowering AL may help prevent PLC, especially in those with moderate genetic susceptibility.
Area of Science:
- Oncology
- Epidemiology
- Physiology
Background:
- Allostatic load (AL) quantifies cumulative physiological stress from chronic stress.
- The relationship between AL, primary liver cancer (PLC) risk, and genetic factors is not well understood.
- Understanding these links is crucial for developing targeted prevention strategies.
Purpose of the Study:
- To investigate the association between allostatic load (AL) and primary liver cancer (PLC) risk.
- To examine potential interactions between AL and genetic susceptibility (polygenic risk score, PRS) in PLC development.
- To identify modifiable factors for PLC prevention.
Main Methods:
- Analysis of 374,632 UK Biobank participants.
- AL assessed via 13 biomarkers; genetic susceptibility via weighted polygenic risk score (PRS).
- Multivariable Cox models and restricted cubic splines used to analyze dose-response relationships and hazard ratios (HRs).
Main Results:
- A significant dose-response relationship between higher AL and increased PLC risk was observed.
- Each 1-unit increase in AL correlated with a 17% higher PLC risk (HR=1.17).
- Individuals in the highest AL quartile had 2.60 times the risk of those in the lowest (HR=2.60). AL's impact was greatest in those with intermediate genetic risk.
Conclusions:
- Cumulative physiological stress (AL) is strongly associated with increased primary liver cancer risk.
- Individuals with intermediate genetic risk represent a key target population for interventions aimed at lowering AL.
- Reducing allostatic load may be a viable strategy for primary liver cancer prevention, particularly in susceptible individuals.
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