{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:08:45Z","timestamp":1788768525988,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Allostatic load (AL) reflects the cumulative physiological burden of chronic stress throughout life, potentially influencing cancer onset and prognosis. However, its association with primary liver cancer (PLC) risk and potential interaction with genetic susceptibility remains unclear. To investigate this, we analyzed 374,632 UK Biobank participants. AL was evaluated using a composite score of 13 cardiovascular, metabolic, and immune biomarkers, while a weighted polygenic risk score (PRS) categorized genetic susceptibility. Multivariable Cox proportional hazards models and restricted cubic splines were utilized to estimate hazard ratios (HRs) and evaluate dose\u2013response relationships. Over a median 12.4\u2010year follow\u2010up, a significant dose\u2013response correlation between AL and PLC risk was observed. In the fully adjusted model, a 1\u2010unit increase in AL was associated with a 17% increased risk (HR\u2009=\u20091.17, 95% CI: 1.12\u20131.23), and participants in the highest AL quartile exhibited a 2.60\u2010times higher risk than those in the lowest (HR\u2009=\u20092.60, 95% CI: 1.72\u20133.95). Despite no multiplicative interaction, stratified analyses revealed AL's impact was most substantial in individuals with intermediate genetic risk (HR\u2009=\u20092.00, 95% CI: 1.38\u20132.90), who constitute the population majority. Additionally, the risk was heightened in overweight\/obese individuals and more pronounced among non\u2010smokers. Ultimately, cumulative physiological stress, indicated by AL, is strongly associated with PLC, supporting the \u201cwear\u2010and\u2010tear\u201d theory of its development. This research highlights a \u201cmalleable zone\u201d in individuals with moderate genetic risk, suggesting that lowering AL may meaningfully aid in preventing PLC.<\/jats:p>","DOI":"10.1002\/ijc.70583","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:51:29Z","timestamp":1784289089000},"page":"2158-2169","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association Between Allostatic Load, Genetic Susceptibility, and Liver Cancer Incidence: A Large\u2010Scale Prospective Cohort Study"],"prefix":"10.1002","volume":"159","author":[{"given":"Danling","family":"Li","sequence":"first","affiliation":[{"name":"Department of Thyroid, Breast and Hernia Surgery, General Surgery The Second Affiliated Hospital of Shantou University Medical College  Shantou Guangdong People's Republic of 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