| Title: | Proteomics of multimorbidity progression across cardiometabolic diseases and cancer in a multinational cohort |
| Journal: | Cardiovascular Diabetology |
| Published: | 20 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42323685/ |
| DOI: | https://doi.org/10.1186/s12933-026-03263-4 |
Publication 20586
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Abstract
BackgroundMultimorbidity, defined here as the co-occurrence of cardiovascular disease (CVD), type 2 diabetes (T2D), and/or cancer is a major public health challenge. However, its underlying biological mechanisms remain unclear, limiting progress toward identifying shared interventional targets.MethodsWe applied large-scale plasma proteomics (SomaScan 7k; 7,289 aptamers) in 13,270 European Prospective Investigation into Cancer and Nutrition (EPIC) participants to identify protein signatures of multimorbidity. We modelled multimorbidity progression as sequential disease transitions, i.e., from the disease-free state at baseline to a first disease and from the first disease to a second disease. Using weighted multivariable Cox regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for risk of cancer, CVD, and T2D. Risk associations were replicated using Olink proteomics in UK Biobank (N = 44,567).ResultsWe identified 422 aptamers associated with more than one disease (FDR-corrected P < 0.05), e.g., 265 aptamers were shared between CVD and T2D. Thirty-eight aptamers were associated with multimorbidity progression. Among these, 27 aptamers showed consistent positive associations across sequential disease transitions, including SEMA6A (disease-free to cancer HR: 1.14; 95% CI 1.05, 1.23; cancer to T2D HR: 2.61; 95% CI 1.76, 3.80). Four aptamers showed consistent inverse associations, including NLGN1 (disease-free to T2D HR: 0.72; 95% CI 0.61, 0.84; T2D to cancer HR: 0.57; 95% CI 0.43, 0.75). Nineteen of the identified proteins were also measured in UK Biobank, with broadly consistent associations.ConclusionsThis study identifies candidate proteins that may indicate molecular pathways to multimorbidity of cardiometabolic diseases and cancer. Future studies should evaluate the causal roles of these proteins for targeted interventions and risk stratification.Graphical abstract</p>
19 Keywords
- Aged
- Biomarkers
- Blood Proteins
- Cardiovascular Diseases
- Diabetes Mellitus, Type 2
- Disease Progression
- Europe
- Female
- Humans
- Male
- Middle Aged
- Multimorbidity
- Neoplasms
- Prognosis
- Prospective Studies
- Proteomics
- Risk Assessment
- Risk Factors
- UK Biobank
16 Authors
- Michael J. Stein
- Vivian Viallon
- Michael F. Leitzmann
- Marc J. Gunter
- Karl Smith-Byrne
- Peggy Ler
- Fulvio Ricceri
- Giovanna Masala
- Sara Beigrezaei
- Yvonne Koop
- Raúl Zamora-Ros
- Ana Jiménez-Zabala
- Christina M. Lill
- Elio Riboli
- Pietro Ferrari
- Heinz Freisling
1 Application
| Application ID | Title |
|---|---|
| 55870 | Obesity and cancer risk and overall and cancer specific mortality: the role of metabolic health and comorbidities |
Enabling scientific discoveries that improve human health