High Serum YKL-40 Levels in Patients with Primary Breast Cancer is Related to Short Recurrence Free Survival

Johansen, Julia S.; Christensen, Ib Jarle; Riisbro, Rikke; Greenall, Michael J.; Chen, Han; Price, Paul A.; Smith, Kelly J.; Brünner, Nils; Harris, Adrian L.

doi:10.1023/a:1024431000710

Cited by 114 publications

(133 citation statements)

References 23 publications

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“…These categories were based on previous studies of cancer and plasma YKL-40 levels. [5][6][7][8]17 Follow up was 100% complete; no participants were lost to follow up. Date of death was obtained from the national Danish Civil Registration System.…”

Section: Endpointsmentioning

confidence: 99%

“…1 Both tumor cells and tumor-associated macrophages produce YKL-40. 2 Plasma YKL-40 is high in patients with gastrointestinal, [3][4][5] breast, 6 lung, 7 prostate 8 and other cancer, [9][10][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.…”

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confidence: 99%

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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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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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Section: Endpointsmentioning

confidence: 99%

mentioning

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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“…One of the mediators that is up-regulated during proinflammatory responses is YKL-40/CHI3L1, which is expressed in the microenvironment of various solid tumors. The expression of YKL-40/CHI3L1 is also up-regulated during tumor growth, and the levels of this glycoprotein have been correlated with poor survival and prognosis in cancer patients [8,9]. YKL-40/CHI3L1, also known as breast regression protein 39, is a member of the 18 glycosyl hydrolase gene family that contains true chitinases and chitinase-like proteins.…”

Section: Introductionmentioning

confidence: 99%

YKL-40/CHI3L1 drives inflammation on the road of tumor progression

Libreros

Iragavarapu-Charyulu

2015

Journal of Leukocyte Biology

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Inflammation plays a vital role at different stages of tumor progression. The development of tumors is affected by inflammatory mediators produced by the tumor and the host. YKL-40/chitinase-3-like-1 protein is often upregulated in inflammation-associated diseases. With the use of chronic inflammatory disease systems, we describe the role of YKL-40/chitinase-3-like-1 protein in enhancing the inflammatory response and its implications in tumorigenesis. We also discuss how pre-existing inflammation enhances tumor growth and metastasis. In this mini-review, we highlight the effect of YKL-40/ chitinase-3-like-1 protein-associated inflammation in promoting tumor progression. J. Leukoc. Biol. 98: 931-936;

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“…Increased serum YKL-40 levels are found in patients with primary and metastatic breast carcinoma [18][19][20] and ovarian carcinoma [21,22], and in preand post-operative samples from patients with colorectal carcinoma [23,24]. It was found in these studies that high serum YKL-40 levels were related to short recurrence-free interval and poor survival of the patients.…”

Section: Introductionmentioning

confidence: 99%

High serum YKL-40 level in patients with small cell lung cancer is related to early death

et al. 2004

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Summary YKL-40, a growth factor for connective tissue cells, is secreted by cancer cells and macrophages. Elevated serum YKL-40 in patients with metastatic carcinoma has been associated with poor prognosis. We evaluated serum YKL-40 in 131 patients with small cell lung cancer (SCLC). Twenty-two percent of the patients with limited disease and 40% of the patients with extensive disease had elevated serum YKL-40. The median survival was 5.1 months for patients with elevated serum YKL-40 and 9.0 months for patients with normal serum YKL-40. Patients with elevated serum YKL-40 had increased hazard for death within the first 6 months after the start of chemotherapy compared to patients with normal serum YKL-40 (HR = 2.06, P = 0.009). Multivariate Cox analysis including routine prognostic variables showed that serum YKL-40 (P = 0.02) is independent of prognostic variables for survival within the first 6 months. Studies are needed to determine the function of YKL-40 in SCLC.

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High Serum YKL-40 Levels in Patients with Primary Breast Cancer is Related to Short Recurrence Free Survival

Cited by 114 publications

References 23 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/CHI3L1 drives inflammation on the road of tumor progression

High serum YKL-40 level in patients with small cell lung cancer is related to early death

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