Early-life undernutrition, immune dysregulation, and cancer incidence in later life: a national life-course analysis from the China health and retirement longitudinal study.
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BACKGROUND: Severe childhood famine may imprint durable immunometabolic scars, yet its longitudinal impact on chronic inflammation and cancer trajectories in China's ageing population is unresolved. METHODS: We analyzed 2-515 adults in the China Health and Retirement Longitudinal Study (2011-2015) who were born 1947-1961; early-life undernutrition was assigned when birth occurred during 1959-1961 and in one of five provinces with > 30% grain deficit. In parallel, an independent hospital-based verification cohort of 82 adults (recruited 2024-2025) 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. RESULTS: Forty-one percent of CHARLS respondents met undernutrition criteria. Compared with unexposed peers, exposed adults showed higher mean hs-CRP (3.18 ± 2.36 vs 2.74 ± 2.11 mg L-¹) and modestly elevated median WBC (6.6 vs 6.3 × 109 L-¹). Undernutrition independently increased the odds of chronic inflammation (hs-CRP ≥ 3 mg L-¹: OR 1.46, 95% CI 1.22-1.75) and leucocytosis (WBC > 10 × 109 L-¹: OR 1.28, 1.04-1.57). Over 9-722 person-years, 122 new cancers occurred; exposed individuals faced a 59% higher hazard (HR 1.59, 1.11-2.27). The verification cohort produced concordant estimates (pooled HR 1.63, 1.23-2.11). Associations were strongest among adults ≥ 60 y or harboring ≥ 2 baseline comorbidities (p-interaction < 0.05). CONCLUSION: 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's cohort of famine-exposed elders expands.