{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:53:21Z","timestamp":1781762001987,"version":"3.54.5"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Severe childhood famine may imprint durable immunometabolic scars, yet its longitudinal impact on chronic inflammation and cancer trajectories in China\u2019s ageing population is unresolved.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed 2\u2013515 adults in the China Health and Retirement Longitudinal Study (2011\u20132015) who were born 1947\u20131961; early-life undernutrition was assigned when birth occurred during 1959\u20131961 and in one of five provinces with &amp;gt; 30% grain deficit. In parallel, an independent hospital-based verification cohort of 82 adults (recruited 2024\u20132025) underwent identical exposure classification, biomarker sampling, and cancer surveillance for external validation. High-sensitivity C-reactive protein (hs-CRP), white-blood-cell (WBC) counts, and physician-confirmed malignancies were the prespecified outcomes. Multivariable logistic and Cox mixed-effects models, with interaction terms, quantified dose-response relations and effect modification; estimates from both cohorts were pooled with inverse-variance weighting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty-one percent of CHARLS respondents met undernutrition criteria. Compared with unexposed peers, exposed adults showed higher mean hs-CRP (3.18 \u00b1 2.36 <jats:italic>vs<\/jats:italic> 2.74 \u00b1 2.11 mg L<jats:sup>-<\/jats:sup>\u00b9) and modestly elevated median WBC (6.6 <jats:italic>vs<\/jats:italic> 6.3 \u00d7 10<jats:sup>9<\/jats:sup> L<jats:sup>-<\/jats:sup>\u00b9). Undernutrition independently increased the odds of chronic inflammation (hs-CRP \u2265 3 mg L<jats:sup>-<\/jats:sup>\u00b9: OR 1.46, 95% CI 1.22\u20131.75) and leucocytosis (WBC &amp;gt; 10 \u00d7 10<jats:sup>9<\/jats:sup> L<jats:sup>-<\/jats:sup>\u00b9: OR 1.28, 1.04\u20131.57). Over 9\u2013722 person-years, 122 new cancers occurred; exposed individuals faced a 59% higher hazard (HR 1.59, 1.11\u20132.27). The verification cohort produced concordant estimates (pooled HR 1.63, 1.23\u20132.11). Associations were strongest among adults \u2265 60 y or harboring \u2265 2 baseline comorbidities (p-interaction &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Developmental caloric deprivation leaves a lasting inflammatory fingerprint that translates into excess mid-life cancer burden. Life-course screening for famine survivors coupled with anti-inflammatory and nutritional interventions will curb malignancy risk as China\u2019s cohort of famine-exposed elders expands.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1602290","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:13:48Z","timestamp":1756268028000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Early-life undernutrition, immune dysregulation, and cancer incidence in later life: a national life-course analysis from the China health and retirement longitudinal 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