Leitzmann, Michael F. and Stein, Michael J. and Baurecht, Hansjoerg and Freisling, Heinz (2025) Excess adiposity and cancer: evaluating a preclinical-clinical obesity framework for risk stratification. ECLINICALMEDICINE, 83: 103247. ISSN , 2589-5370
Full text not available from this repository. (Request a copy)Abstract
Background Obesity is a known cancer risk factor, yet its classification by body mass index fails to capture organ dysfunction. Methods In 459,342 UK Biobank participants enrolled between 2006 and 2010, we applied the Lancet Diabetes and Endocrinology Commission's definitions of preclinical (excess adiposity without organ dysfunction) and clinical obesity (with organ dysfunction) to prospectively assess associations with 28 cancers. Multivariable Cox regression estimated hazard ratios and 95% confidence intervals for each obesity classification and cancer type. Findings During 11.6 years of follow-up, 47,060 incident cancer cases were identified. Preclinical obesity was positively associated with 11 cancer types across multiple organ systems, including cancers of the digestive (esophageal adenocarcinoma, gastric cardia, liver, biliary tract, pancreas, colorectum), reproductive (endometrium, postmenopausal breast, fatal prostate), urinary (kidney), and endocrine (thyroid) systems. Clinical obesity was positively associated with 12 cancers, showing stronger relations particularly for metabolically driven malignancies such as hepatocellular carcinoma and endometrial, colorectal, and pancreatic cancers. It was also positively associated with lung cancer. Conversely, preclinical and clinical obesity were inversely associated with non-fatal prostate cancer, suggesting a distinct underlying mechanism. We estimate that in the UK Biobank cohort, preclinical obesity accounted for 5.5% (4.7, 6.3) and clinical obesity for 4.3% (3.6, 4.9) of obesity-related cancer. Interpretation The link between preclinical obesity and increased cancer risk suggests that obesity-related carcinogenesis begins before clinically detectable abnormalities, highlighting the need for early risk identification. Stronger associations with clinical obesity, particularly in metabolically driven cancers, reinforce the role of organ dysfunction in exacerbating carcinogenesis, emphasizing medical monitoring and intervention. Funding Funding for IIG_FULL_2021_027 was obtained from World Cancer Research Fund (WCRF UK), as part of the World Cancer Research Fund International grant programme. This study was supported by the French National Cancer Institute (l'Institut National du Cancer, INCA_16824) and the German Research Foundation (BA 5459/2-1). Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BODY FATNESS; ASSOCIATION; Clinical obesity; Cancer risk; Cohort study |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Sep 2026 12:22 |
| Last Modified: | 23 Sep 2026 12:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/66476 |
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