Abstract
Given global population aging and the absence of aging-reversal therapies, elucidating the aging-related cancer risk association and developing cancer prevention strategies are imperative. This population-based cohort study analyzed data from the UK Biobank. Aging was assessed through four validated markers, including Klemera-Doubal method (KDM), PhenoAge, leukocyte telomere length (TL) and chronological age. Over a median follow-up of 13.5 years, significant associations between all aging measures and elevated overall cancer risk were observed. False discovery rate (FDR)-corrected analyses revealed a significant association in a biological aging group for seven site-specific cancers, including esophageal, colorectal, pancreatic, skin, kidney, urinary tract cancers, and lymphoma, as evaluated by the four aging markers. A significant interaction (FDR-corrected p < 0.05) between Life's Essential 8 (LE8) and PhenoAge was observed for lung cancer risk. Furthermore, joint analyses revealed that elevated LE8 scores modify this risk for overall cancer among individuals with biological aging, with consistent risk reductions observed for esophageal, gastric, breast, and uterine cancers across all aging markers. These findings suggest that a higher LE8 score is associated with lower cancer risk in the context of biological aging.
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Data availability
Due to the privacy and sensitive information contained in the data, the data used for this study will not be made publicly available. The raw and derived data from UK Biobank are available to approved investigators (https://www.ukbiobank.ac.uk/). All relevant data will be shared on reasonable request to the corresponding authors.
Code availability
Codes used for this study are available upon reasonable request from the authors.
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Acknowledgements
We are grateful to the participants and study staff of UK Biobank. This research received no external funding.
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Y.L., Z.X., X.G., and H.F. contributed to the conception and design of this study. Z.X., W.Z., X.G., Y.Z., S.Y., Z.J., Y.H., and J.Z. were involved in the acquisition of data. Z.X., H.F., and J.L. performed analysis. Z.X., H.F., and J.L. were involved in data interpretation. Y.Z.., H.F., W.Z., and J.L. wrote the first draft of the manuscript. All the authors discussed the results, revised the manuscript, and agreed to its publication. H.F. and Y.L. supervised the study.
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Li, J., Zhang, Y., Zhang, W. et al. Aging and increased cancer risk: exploring the potential of LE8 score to mitigate risk. npj Aging (2026). https://doi.org/10.1038/s41514-026-00352-2
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DOI: https://doi.org/10.1038/s41514-026-00352-2
