medwireNews: Elevated levels of the inflammatory biomarker YKL-40 are associated with a significantly increased risk for obesity-related and gastrointestinal cancers, particularly liver cancer, in people with type 2 diabetes, study findings indicate.
Writing in the British Journal of Cancer, Alisa Kjaergaard (Aarhus University Hospital, Denmark) and co-authors explain that YKL-40, also known as chitinase-3-like protein, is produced locally at inflammation sites by cells such as tumor-associated macrophages and cancer cells. It is elevated in many cancers and studies have also shown that people with type 2 diabetes have consistently higher YKL-40 levels than healthy controls.
However, researchers have not previously investigated how YKL-40 levels are associated with future cancer risk in people with type 2 diabetes.
To address this, Kjaergaard and team analyzed data for 11,346 individuals with newly diagnosed type 2 diabetes who were followed up for a median of 9 years.
During this period, 362 participants developed obesity-related cancers, 329 of which were gastrointestinal cancers, including 204 colorectal cancers, 56 liver cancers, and 46 pancreatic cancers. There were also 78 lung cancer events and 42 bladder cancer events as well as 202 prostate, 141 breast, 46 ovarian, and 15 uterine cancer events recorded.
At baseline, the mean YKL-40 level was 63 µg/L overall, increasing from 22 µg/L in the lowest of five percentiles (0–33%) to 329 µg/L in the highest percentile (96–100%).
The researchers report that elevated YKL-40 levels were associated with longer diabetes duration, higher BMI and waist-to-hip ratio, alcohol overconsumption, smoking, lower physical activity, higher glycated hemoglobin, lower insulin sensitivity, lower kidney function, and higher triglyceride and C-reactive protein (CRP) levels.
After adjustment for age, sex, family history of type 2 diabetes, type 2 diabetes duration, waist-to-hip ratio, alcohol overconsumption and physical activity, the researchers found that individuals in the highest percentile of YKL-40 level had a significant 2.4-fold increased risk for obesity-related cancers and a significant 2.6-fold increased risk for gastrointestinal cancers relative to those in the lowest percentile group.
Among the individual cancers, the risk for liver cancer was a significant 44.2-fold higher in people with the highest versus lowest YKL-40 levels while the risk for bladder cancer was a significant 4.2-fold higher.
Conversely, there was no significant association between YKL-40 level and the risk for colorectal cancer, lung cancer, and cancers of the reproductive organs.
When the researchers compared the prognostic performance of YKL-40 to that of CRP, they found that each standard deviation (SD) increase in YKL-40 and CRP levels was associated with similarly increased hazard ratios (HRs) for obesity-related and gastrointestinal cancers.
The HRs were higher for YKL-40 than for CRP for liver and bladder cancers, whereas each SD increase in CRP levels was associated with a higher HR for lung, colorectal cancer, and ovarian cancer than each SD increase in YKL-40.
“These findings indicate that YKL-40 and CRP have distinct prognostic roles in different cancer types among individuals with type 2 diabetes,” Kjaergaard et al remark. They continue: “YKL-40, in particular, shows strong precision medicine potential as a biomarker for liver cancer, supporting its use in early detection and focused monitoring in this population.”
The authors also caution that the associations they observed “may be due to reverse causation, where undiagnosed cancer raises YKL-40 and CRP levels.”
However, they say that “this does not explain all cancer events, as half occurred four to five years after enrolment. A more likely explanation is that inflammation, which increases both YKL-40 and CRP levels, could be the underlying cause, as both biomarkers are linked to cancer risk.”
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