| Title: | Phenotypic age acceleration and early-onset lung cancer: a case-control and prognostic cohort study involving multiple clinical centres with validation in the UK Biobank |
| Journal: | EBioMedicine |
| Published: | 10 Feb 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41671868/ |
| DOI: | https://doi.org/10.1016/j.ebiom.2026.106162 |
Publication 18311
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Abstract
BACKGROUND: Lung cancer is mainly diagnosed in elderly adults, yet the incidence of early-onset disease in people aged ≤45 years is increasing. Current screening strategies largely target elder populations, leaving younger individuals at risk of delayed diagnosis and adverse outcomes. Phenotypic Age Acceleration (PhenoAgeAccel), which indicates the difference between biological age and chronological age, has been associated with cancer susceptibility, but its role in early-onset lung cancer is unclear.</p>
METHODS: We performed a case-control and prognostic cohort study in China, including 222 early-onset lung cancer patients and 222 age- and sex-matched healthy volunteers, and externally validated findings in the UK Biobank. PhenoAgeAccel was calculated from routinely available haematological and biochemical markers. Logistic regression models estimated associations between PhenoAgeAccel and lung cancer risk. Survival analyses assessed the relationship between PhenoAgeAccel and overall survival among early-onset patients.</p>
FINDINGS: Early-onset lung cancer patients had substantially higher PhenoAgeAccel than matched controls (P < 0.001). PhenoAgeAccel was associated with a dose-dependent increase in early-onset lung cancer risk (odds ratio [OR] = 1.18; 95% CI: 1.14-1.23). Subgroup analyses by chronological age demonstrated a stronger association in earlier adulthood, whereas associations among elder adults (≥65 years) were not significant. In early-onset patients, higher PhenoAgeAccel predicted worse overall survival (hazard ratio [HR] = 2.17; 95% CI: 1.20-3.93). Results were corroborated in the UK Biobank cohort.</p>
INTERPRETATION: PhenoAgeAccel is positively associated with both a greater risk of early-onset lung cancer and poorer prognosis, supporting its potential utility for early detection and risk stratification in younger populations.</p>
FUNDING: National Natural Science Foundation of China (no. 82303969); Beijing Xisike Clinical Oncology Research Foundation (no. Y-2024AZ [EGFR]MS-0079); Beijing Natural Science Foundation (no. 7222144).</p>
18 Keywords
- Adult
- Age Factors
- Age of Onset
- Aged
- Biological Specimen Banks
- Case-Control Studies
- China
- Cohort Studies
- Female
- Humans
- Lung Neoplasms
- Male
- Middle Aged
- Phenotype
- Prognosis
- Risk Factors
- UK Biobank
- United Kingdom
17 Authors
- Ruolin Gao
- Yuxuan Liao
- Qiwen Zheng
- Zhijian Xu
- Xiaowei Zhao
- Qinxiang Guo
- Zhijie Wang
- Jianchun Duan
- Rui Wan
- Jiachen Xu
- Kailun Fei
- Boyang Sun
- Wei Zhuang
- Hua Bai
- Yanhui Cheng
- Jia Zhong
- Jie Wang
1 Application
| Application ID | Title |
|---|---|
| 104784 | Phenotypic and genetic associations between chronic diseases in the UK Biobank cohort. |
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