Plasma YKL-40 and Total and Disease-Specific Mortality in the General Population

Plasma YKL-40 is high in patients with cancer and in individuals who later develop cancer. Whether YKL-40 is only a marker or indeed a cause of cancer is presently unknown. We tested the hypothesis that observationally and genetically, high plasma YKL-40 is associated with high risk of cancer. For this purpose, we performed cohort and Mendelian randomization studies in 96,099 individuals from the Danish general population. Plasma levels of YKL-40 were measured in 21,643 and CHI3L1 rs4950928 was genotyped in 94,568 individuals. From 1943 through 2011, 2,291 individuals developed gastrointestinal cancer, 913 developed lung cancer, 2,863 women developed breast cancer, 1,557 men developed prostate cancer and 5,146 individuals developed other cancer. Follow-up was 100% complete. Multifactorially and CRP adjusted hazard ratio (HR) for gastrointestinal cancer was 1.82 (95%CI, 1.16-2.86) for 96-100% versus 0-33% YKL-40 percentile category. Corresponding HR were 1.71 (0.95-3.07) for lung cancer, but insignificant for breast cancer, prostate cancer and other cancers. CHI3L1 rs4950928 genotype was associated with plasmaYKL-40 levels, but not with risk of any cancer category. For gastrointestinal cancer, a doubling in YKL-40 was associated with a multifactorially and CRP adjusted observational HR of 1.14(1.05-1.23) for gastrointestinal cancer, but a corresponding genetic odds ratio of 1.06(0.94-1.18). For lung cancer, corresponding risk estimates were 1.11(1.00-1.22) observationally and 1.01(0.84-1.20) genetically. For other cancer categories, observational and genetic findings were insignificant. This study shows that high plasma YKL-40 levels were associated with high risk of gastrointestinal and likely of lung cancer, but genetic high levels were not.Inflammation plays an important role in cancer development and/or progression. 1 Both tumor cells and tumor-associated macrophages produce YKL-40. 2 Plasma YKL-40 is high in patients with gastrointestinal, 3-5 breast, 6 lung, 7 prostate 8 and other cancer, 9-11 and is also associated with tumour burden and prognosis after a cancer diagnosis. 5,[12][13][14][15][16] Furthermore, high plasma YKL-40 predicts high risk of gastrointestinal cancer in the general population. 17 Whether YKL-40 is only a marker of inflammation and cancer or plays a causal role in the development of cancer is presently unknown.A single nucleotide polymorphism in the proximal promoter of chitinase-3-like-1 (same as YKL-40; CHI3L1), rs4950928, accounts for 9.4% of the variance of plasma YKL-40. 18 MYC/MAX transcriptional factors bind better to the major than to the minor allele of rs4950928 in the gene promoter, 19 thereby presumably increasing CHI3L1 transcription and elevating plasma YKL-40 levels in carriers of the major versus minor allele. [20][21][22] We tested the hypothesis that observationally and genetically high plasma YKL-40 is associated with high risk of cancer. For this purpose, we performed cohort and Mendelian randomization studies in 96,099 individuals from the Danish general population...

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“…Plasma YKL-40 levels were analysed in samples frozen for 12-15 years and stored at 2808C in 8,443 of these participants. 26,27 The CGPS study…”

Section: The Cchs Studymentioning

confidence: 99%

“…17,27 Because plasma YKL-40 increases with increasing age, YKL-40 percentile categories allowed for age differences (Supporting Information Fig. S1).…”

Section: Plasma Ykl-40 Levelsmentioning

confidence: 99%

Observational and genetic plasma YKL‐40 and cancer in 96,099 individuals from the general population

Kjærgaard

Nordestgaard

Johansen

et al. 2015

Intl Journal of Cancer

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“…We stratified plasma YKL-40 concentrations into 5 percentile categories to evaluate both tertiles in the lower range and extreme phenotypes in the upper range; the latter was a priori presumed to infer increased risk and was identical to previous reports (21,22 ): 0%-33%, 34%-66%, 67%-90%, 91%-95%, and 96%-100%. Because plasma YKL-40 increases with increasing age, YKL-40 percentile categories al-lowed for age differences (see online Supplemental Fig.…”

Section: Plasma Ykl-40 Concentrationsmentioning

confidence: 99%

YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population: Cohort and Mendelian Randomization Studies

et al. 2014

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“…High plasma YKL-40 levels in subjects from the general population associate with increased risk of developing (4) and death from gastrointestinal cancer (5). In this study population, we also examined plasma C-reactive protein (CRP) and YKL-40 levels simultaneously and observed that elevated YKL-40 levels were associated with an increased risk of gastrointestinal cancer, independently of CRP levels (6).…”

Section: Introductionmentioning

confidence: 95%

Serum YKL-40 in Risk Assessment for Colorectal Cancer: A Prospective Study of 4,496 Subjects at Risk of Colorectal Cancer

Johansen

Christensen

Jørgensen

et al. 2015

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The aim of the present study was to test the hypothesis that high serum YKL-40 associates with colorectal cancer in subjects at risk of colorectal cancer. We measured serum YKL-40 in a prospective study of 4,496 Danish subjects [2,064 men, 2,432 women, median age 61 years (range, 18-97)] referred to endoscopy due to symptoms or other risk factors for colorectal cancer. Blood samples were collected just before large bowel endoscopy. Serum YKL-40 was determined by ELISA. Serum YKL-40 was higher (P < 0.0001, unadjusted for confounding covariates) in subjects . Multivariable analysis (YKL-40, CEA, age, gender, body mass index, and center) showed that serum YKL-40 was a predictor for colorectal cancer in individuals without comorbidity (OR, 1.25; 95% CI, 1.05-1.40; P ¼ 0.012), whereas this was not the case for those with comorbidity (OR, 0.98; 95% CI, 0.84-1.14; P ¼ 0.80). In conclusion, high serum YKL-40 in subjects suspected of colorectal cancer and without comorbidity associates with colorectal cancer. Determination of serum YKL-40 may be useful in combination with other biomarkers in risk assessment for colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 621-6. Ó2015 AACR.

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Plasma YKL-40 and Total and Disease-Specific Mortality in the General Population

Cited by 60 publications

References 26 publications

Observational and genetic plasma YKL‐40 and cancer in 96,099 individuals from the general population

Observational and genetic plasma YKL‐40 and cancer in 96,099 individuals from the general population

YKL-40 and Alcoholic Liver and Pancreas Damage and Disease in 86258 Individuals from the General Population: Cohort and Mendelian Randomization Studies

Serum YKL-40 in Risk Assessment for Colorectal Cancer: A Prospective Study of 4,496 Subjects at Risk of Colorectal Cancer

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