Evidence map›Paper›PMID 42323685›Full record

ArticleCardiovascular diabetology2026

Proteomics of multimorbidity progression across cardiometabolic diseases and cancer in a multinational cohort.

Michael J Stein, Vivian Viallon, Michael F Leitzmann, Marc J Gunter, Karl Smith-Byrne, Peggy Ler, Fulvio Ricceri, Giovanna Masala, Sara Beigrezaei, Yvonne Koop and 6 more

Abstract readMulticenter Study
In one paragraph

Article in Cardiovascular diabetology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Michael J SteinDepartment of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany. michael.stein@helmholtz-munich.de.ORCID 0000-0002-1120-1751
Vivian ViallonInternational Agency for Research on Cancer (IARC), Nutrition and Metabolism Branch, 25 avenue Tony Garnier, CS90627, Lyon, 69366, France.
Michael F LeitzmannDepartment of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany.
Marc J GunterCancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College, London, UK.
Karl Smith-ByrneCancer Epidemiology Unit, Oxford Population Health, University of Oxford, Oxford, UK.
Peggy LerInternational Agency for Research on Cancer (IARC), Nutrition and Metabolism Branch, 25 avenue Tony Garnier, CS90627, Lyon, 69366, France.
Fulvio RicceriDepartment of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology, and Public Health (C- BEPH), University of Turin, Turin, Italy.
Giovanna MasalaClinical Epidemiology Unit, Institute for cancer research, prevention and clinical network (ISPRO), Florence, Italy.
Sara BeigrezaeiDepartment Global Public Health & Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
Yvonne KoopDepartment Epidemiology and Health Economics, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.
Raúl Zamora-RosUnit of Nutrition and Cancer, Institut d'Investigació Biomèdica de Bellvitge, Gran Via de l'Hospitalet, 199, 08908, L'Hospitalet de Llobregat, Barcelona, España.
Ana Jiménez-ZabalaMinistry of Health of the Basque Government, Sub-Directorate for Public Health and Addictions of Gipuzkoa, San Sebastián, Gipuzkoa, Spain.
Christina M LillCancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College, London, UK.
Elio RiboliCancer Epidemiology and Prevention Research Unit, School of Public Health, Imperial College, London, UK.
Pietro Ferrari *International Agency for Research on Cancer (IARC), Nutrition and Metabolism Branch, 25 avenue Tony Garnier, CS90627, Lyon, 69366, France.
Heinz Freisling *International Agency for Research on Cancer (IARC), Nutrition and Metabolism Branch, 25 avenue Tony Garnier, CS90627, Lyon, 69366, France. freislingh@iarc.who.int.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Blood ProteinsCardiovascular DiseasesDiabetes Mellitus, Type 2NeoplasmsProteomicsAgedBiomarkersDisease ProgressionEuropeFemaleHumansMaleMiddle AgedMultimorbidityPrognosisProspective StudiesBiomarkersBlood ProteinsCancerCardiometabolic diseaseMultimorbidityProteomics

Identifiers

PMID42323685
PMCPMC13288577

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.