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

**Authors:** Alisa D. Kjaergaard, Allan A. Vaag, Verena H. Jensen, Michael H. Olsen, Kurt Højlund, Peter Vestergaard, Torben Hansen, Reimar W. Thomsen, Niels Jessen

PMC · DOI: 10.1038/s41416-025-02996-5 · British Journal of Cancer · 2025-04-05

## TL;DR

This study found that high levels of the YKL-40 biomarker are strongly linked to increased risks of liver and bladder cancers in people with early type 2 diabetes.

## Contribution

The study identifies YKL-40 as a more effective biomarker than CRP for predicting liver and bladder cancer risks in early type 2 diabetes patients.

## Key findings

- YKL-40 levels were strongly associated with increased risks of liver and bladder cancers.
- YKL-40 outperformed CRP in predicting liver and bladder cancer risks.
- CRP was a better predictor for lung, colorectal, and ovarian cancers.

## Abstract

We examined the association of serum YKL-40, an inflammatory biomarker, with incident cancer risk in early type 2 diabetes.

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.

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.

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.

## Linked entities

- **Proteins:** CHI3L1 (chitinase 3 like 1), CRP (C-reactive protein)
- **Diseases:** type 2 diabetes (MONDO:0005148), liver cancer (MONDO:0002691), bladder cancer (MONDO:0004986), lung cancer (MONDO:0005138), colorectal cancer (MONDO:0005575), ovarian cancer (MONDO:0005140)

## Full-text entities

- **Genes:** CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, CHI3L1 (chitinase 3 like 1) [NCBI Gene 1116] {aka ASRT7, CGP-39, GP-39, GP39, HC-gp39, HCGP-3P}
- **Diseases:** liver and bladder cancers (MESH:D006528), gastrointestinal cancers (MESH:D005770), cancer (MESH:D009369), bladder cancers (MESH:D001749), liver (MESH:D017093), type 2 diabetes (MESH:D003924), gastrointestinal, liver, pancreatic, colorectal, bladder and lung cancers (MESH:D015179), lung, colorectal, and ovarian cancers (MESH:D010051), inflammatory (MESH:D007249), obesity (MESH:D009765)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12119867