ORIGINAL RESEARCH article
Front. Immunol.
Sec. Nutritional Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1602290
This article is part of the Research TopicNutritional Impacts on Human Tumor Development and Immune SystemView all 10 articles
Early-Life Undernutrition, Immune Dysregulation, and Cancer Incidence in Later Life: A National Life-Course Analysis from the China Health and Retirement Longitudinal Study
Provisionally accepted
- 1Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China
- 2Southwest Medical University, Luzhou, China
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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.We analysed 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,). The verification cohort produced concordant estimates (pooled HR 1.63,). Associations were strongest among adults ≥ 60 y or harbouring ≥ 2 baseline comorbidities (p-interaction < 0.05).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.
Keywords: Early-life undernutrition, Cancer Incidence, Childhood famine exposure, Nutritional deprivation, Immune function, chronic inflammation
Received: 29 Mar 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Wang, Wu, Zhou, Huang, Li and Tang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xuancheng Zhou, Southwest Medical University, Luzhou, China
Gang Huang, Southwest Medical University, Luzhou, China
Jingdong Li, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China
Xiaowei Tang, Southwest Medical University, Luzhou, China
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