Systemic inflammation mediates the link between metabolic syndrome and colorectal cancer risk: insights from a large prospective cohort

This study confirms that both MetS and systemic inflammation contribute to increased CRC risk, with inflammation playing a significant mediating role. These findings provide novel insights into underlying mechanisms and highlight the potential of inflammation biomarkers, particularly IBI, for improving early CRC risk prediction in individuals with metabolic dysfunction. Key messages What is already known on this topic: Metabolic syndrome (MetS) is associated with an increased colorectal cancer (CRC) risk, but the biological pathway remains incompletely understood. Systemic low-grade inflammation has been proposed as a mediator, yet composite inflammation indices are underexplored. What this study adds: In 335 544 UK Biobank participants, MetS was associated with a higher risk of CRC (HR = 1.11, 95% CI 1.03-1.20). Five systemic inflammation biomarkers (NLR, PLR, SII, SIRI, and IBI) were associated with both MetS and CRC. Mediation analysis indicated partial mediation, with IBI contributing the largest proportion (16.6%). How this study might affect research, practice, or policy: Incorporating systemic inflammation indices, particularly IBI, may improve early risk stratification for CRC among individuals with MetS. These findings support the development of prevention strategies targeting low-grade inflammation, while guiding future mechanistic and translational research.