| Title: | Biological aging and generational shifts in early-onset cancer risk |
| Journal: | Nature Medicine |
| Published: | 22 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42332142/ |
| DOI: | https://doi.org/10.1038/s41591-026-04448-w |
| URL: | https://www.nature.com/articles/s41591-026-04448-w.pdf |
Publication 20581
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Abstract
Incidence of early-onset cancer is rising globally in recent generations, which underscores the need to elucidate the influence of emerging generational risk factors. Systemic and organ-specific aging reflects the cumulative impact of exposures and may provide an integrative and complementary approach to understand early-onset cancer risk. Here among 154,169 young adults from the United Kingdom Biobank, systemic aging measured by PhenoAge increased across birth cohorts, with 23% s.d. increase for those born 1965-1974 versus 1950-1954, and was associated with early-onset solid cancer risk (hazard ratio (HR)per s.d. 1.08; 95% confidence interval (CI), 1.03-1.13), driven by lung, gastrointestinal and uterine cancers, independent of genetic risks of aging and cancer. Patterns were consistent using alternative systemic aging measures, including the Klemera-Doubal method-defined age gap and metabolomic-based age gap. These findings were validated partially among 10,262 participants in the United States All of Us Research Program. Proteomics-based organ-specific aging analyses linked immune aging with early-onset lung cancer (HRper s.d. 1.89; CI, 1.20-2.97) and adipose tissue aging to early-onset colorectal cancer (HR 1.60; CI, 1.11-2.32). Greater age gap, reflecting more advanced biological aging relative to chronological age, may serve as a driver associated with risk of early-onset solid cancers, highlighting the importance of uncovering underlying mechanisms to guide effective prevention strategies.</p>
9 Authors
- Ruiyi Tian
- Xiaoyu Zong
- Duo Ren
- Stefani Tica
- Daniel Hong
- Oluseye Oduyale
- Jason D. Buenrostro
- Ramaswamy Govindan
- Yin Cao
1 Application
| Application ID | Title |
|---|---|
| 55288 | Early life, adulthood, and genomic risk factors for early-onset cancers |
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