YKL-40 and risk of incident cancer in early type 2 diabetes: a Danish cohort study

Background: We examined the association of serum YKL-40, an inflammatory biomarker, with incident cancer risk in early type 2 diabetes. Methods: A cohort of 11,346 individuals newly diagnosed with type 2 diabetes was followed for up to 14 years. YKL-40 levels (n = 9010) were categorised into five percentiles (0-33%, 34-66%, 67-90%, 91-95%, and 96-100%), and baseline YKL-40 and CRP (n = 9644) were analyzed continuously (per 1 SD log increment) for comparison. Cox regression models assessed associations with obesity-related, gastrointestinal, liver, pancreatic, colorectal, bladder and lung cancers, as well as cancers of reproductive organs. Results: Adjusted HRs (95% CIs) for the highest versus lowest YKL-40 category were 2.4 (1.6-3.7) for obesity-related, 2.6 (1.7-4.1) for gastrointestinal, 44.2 (12.8-153.4) for liver, and 4.2 (1.3-14.1) for bladder cancers. No associations were found for other cancers. YKL-40 and CRP had similar prognostic abilities for obesity-related and gastrointestinal cancers, but YKL-40 outperformed CRP for liver and bladder cancers. Conversely, CRP was a stronger predictor for lung, colorectal, and ovarian cancers. Discussion: YKL-40 was associated with the risks of liver and bladder cancers, clearly outperforming CRP for these cancers. This suggests distinct prognostic roles for YKL-40 and CRP, and highlights YKL-40 as a promising biomarker for liver cancer.