Cardiovascular-Kidney-Metabolic Syndrome Staging and Cancer Risk: Insights From Proteomic and Metabolomic Mediators
Authors' conclusion
CKM staging is associated with incremental cancer risk and stage-specific immune-metabolic pathways, highlighting potential prevention targets.
Study context
- Population
- UK Biobank participants
- Exposure
- Cardiovascular-kidney-metabolic (CKM) stages 1–4 vs stage 0
- Outcome
- Overall cancer incidence
Methodological detailsmultiomics mediation analysis
- Multiomics mediation analysis
Main finding
As reported in the abstract
Overall cancer risk
- Overall cancer risk increased stepwise from CKM stages 1 to 3, with slight attenuation but persistent elevation in stage 4
Observational data: associations, not effects.
Further findings
Stage-specific proteomic mediators and mechanisms
- Stage 1: leukocyte/lymphocyte activation and cell-cell adhesion
- Stage 2: T cell-related immunity and emerging immune tolerance induction
- Stage 3: emerging natural killer (NK) cell tolerance induction and respiratory burst in the inflammatory response
- Stage 4: dominant NK cell tolerance induction and tissue-resident chronic pathology
Metabolomic mediation
- Dominant metabolomic mediation evolved from high-density lipoproteins (HDLs) and triglyceride-rich lipoproteins (TRLs) to low-density lipoproteins (LDLs)
Original publication
Cardiovascular-Kidney-Metabolic Syndrome Staging and Cancer Risk: Insights From Proteomic and Metabolomic Mediators. JACC CardioOncol. Published 14 July 2026. doi:10.
Summarised from the published abstract; every number is checked against it