Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals

Hans J Nielsen; Nils Brünner; Lars Nannestad Jørgensen; Jesper Olsen; Hans B Rahr; Knud Thygesen; Ute Hoyer; Søren Laurberg; Petra Stieber; Marinus A Blankenstein; Gerard Davis; Barry L Dowell; Ib J Christensen; NN NN; Lars Nannestad Jørgensen; Jesper Arnold Olsen

doi:10.3109/00365521.2010.513060

Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals

Hans J Nielsen, Nils Brünner, Lars Nannestad Jørgensen, Jesper Olsen, Hans B Rahr, Knud Thygesen, Ute Hoyer, Søren Laurberg, Petra Stieber, Marinus A Blankenstein, Gerard Davis, Barry L Dowell, Ib J Christensen, NN NN, Lars Nannestad Jørgensen, Jesper Arnold Olsen

Department of Clinical Medicine

57 Citations (Scopus)

Abstract

Objective. The combination of plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) and carcinoembryonic antigen (CEA) may be valuable biomarkers for early detection of colorectal cancer (CRC). A prospective, population based study was performed to validate this hypothesis. Material and methods. Individuals (n =4509) referred for large bowel endoscopy due to symptoms of CRC were prospectively included. Baseline data and concurrent diseases were recorded. The primary endpoint was detection of CRC and findings at examinations were recorded using International Classification of Diseases-10 codes. Plasma was obtained before endoscopy and TIMP-1 and CEA levels were determined after the inclusion of all individuals. Results. Findings were based on sigmoidoscopy in 1766 and colonoscopy in 2743 individuals. Colon cancer (CC) was detected in 184 and rectal cancer in 110 individuals. Ten individuals with other cancers, 856 with adenomas and 1176 with non-neoplastic findings were also detected. The biomarker levels were increased in a variety of diseases including CRC compared to individuals without any findings at endoscopy. A multivariable analysis demonstrated that both markers were significant and independent detectors of CRC. Combining both biomarkers, independent contributions from each (TIMP-1, odds ratio (OR) =1.8 (95% confidence interval (CI): 1.4-2.2), p < 0.0001; CEA < 5 ng/ml, OR= 1.6, 1.3-1.9, or ≥5 ng/ml, OR =2.3, 95% CI: 1.9-2.7 (p < 0.0001)) were obtained. Subgroup analysis of individuals examined by colonoscopy with CC as the endpoint showed that combining both biomarkers, independent contributions from each (TIMP-1, OR= 2.5, 95% CI: 1.8-3.4, p < 0.0001; CEA < 5 ng/ml, OR =1.4, 95% CI: 1.1-1.8, and CEA ≥ 5 ng/ml, OR= 2.3, 95% CI: 1.8-3.0 (p < 0.0001)) were obtained. Conclusions. This prospective validation study supports the use of the combination of plasma TIMP-1 and CEA protein measurements as a potential aid in early detection of CRC and specifically of CC.

Original language	English
Journal	Scandinavian Journal of Gastroenterology
Volume	46
Issue number	1
Pages (from-to)	60-69
Number of pages	9
ISSN	0036-5521
DOIs	https://doi.org/10.3109/00365521.2010.513060
Publication status	Published - Jan 2011

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10.3109/00365521.2010.513060

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Nielsen, H. J., Brünner, N., Jørgensen, L. N., Olsen, J., Rahr, H. B., Thygesen, K., Hoyer, U., Laurberg, S., Stieber, P., Blankenstein, M. A., Davis, G., Dowell, B. L., Christensen, I. J., NN, NN., Jørgensen, L. N., & Olsen, J. A. (2011). Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals. Scandinavian Journal of Gastroenterology, 46(1), 60-69. https://doi.org/10.3109/00365521.2010.513060

Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals. / Nielsen, Hans J; Brünner, Nils; Jørgensen, Lars Nannestad et al.

In: Scandinavian Journal of Gastroenterology, Vol. 46, No. 1, 01.2011, p. 60-69.

Research output: Contribution to journal › Journal article › Research › peer-review

Nielsen, HJ, Brünner, N, Jørgensen, LN, Olsen, J, Rahr, HB, Thygesen, K, Hoyer, U, Laurberg, S, Stieber, P, Blankenstein, MA, Davis, G, Dowell, BL, Christensen, IJ, NN, NN, Jørgensen, LN & Olsen, JA 2011, 'Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals', Scandinavian Journal of Gastroenterology, vol. 46, no. 1, pp. 60-69. https://doi.org/10.3109/00365521.2010.513060

@article{8c89707b47034e59aca9ba79fa750db7,

title = "Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals",

abstract = "Objective. The combination of plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) and carcinoembryonic antigen (CEA) may be valuable biomarkers for early detection of colorectal cancer (CRC). A prospective, population based study was performed to validate this hypothesis. Material and methods. Individuals (n =4509) referred for large bowel endoscopy due to symptoms of CRC were prospectively included. Baseline data and concurrent diseases were recorded. The primary endpoint was detection of CRC and findings at examinations were recorded using International Classification of Diseases-10 codes. Plasma was obtained before endoscopy and TIMP-1 and CEA levels were determined after the inclusion of all individuals. Results. Findings were based on sigmoidoscopy in 1766 and colonoscopy in 2743 individuals. Colon cancer (CC) was detected in 184 and rectal cancer in 110 individuals. Ten individuals with other cancers, 856 with adenomas and 1176 with non-neoplastic findings were also detected. The biomarker levels were increased in a variety of diseases including CRC compared to individuals without any findings at endoscopy. A multivariable analysis demonstrated that both markers were significant and independent detectors of CRC. Combining both biomarkers, independent contributions from each (TIMP-1, odds ratio (OR) =1.8 (95% confidence interval (CI): 1.4-2.2), p < 0.0001; CEA < 5 ng/ml, OR= 1.6, 1.3-1.9, or ≥5 ng/ml, OR =2.3, 95% CI: 1.9-2.7 (p < 0.0001)) were obtained. Subgroup analysis of individuals examined by colonoscopy with CC as the endpoint showed that combining both biomarkers, independent contributions from each (TIMP-1, OR= 2.5, 95% CI: 1.8-3.4, p < 0.0001; CEA < 5 ng/ml, OR =1.4, 95% CI: 1.1-1.8, and CEA ≥ 5 ng/ml, OR= 2.3, 95% CI: 1.8-3.0 (p < 0.0001)) were obtained. Conclusions. This prospective validation study supports the use of the combination of plasma TIMP-1 and CEA protein measurements as a potential aid in early detection of CRC and specifically of CC.",

author = "Nielsen, {Hans J} and Nils Br{\"u}nner and J{\o}rgensen, {Lars Nannestad} and Jesper Olsen and Rahr, {Hans B} and Knud Thygesen and Ute Hoyer and S{\o}ren Laurberg and Petra Stieber and Blankenstein, {Marinus A} and Gerard Davis and Dowell, {Barry L} and Christensen, {Ib J} and NN NN and J{\o}rgensen, {Lars Nannestad} and Olsen, {Jesper Arnold}",

year = "2011",

month = jan,

doi = "10.3109/00365521.2010.513060",

language = "English",

volume = "46",

pages = "60--69",

journal = "Scandinavian Journal of Gastroenterology",

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publisher = "Taylor & Francis",

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TY - JOUR

T1 - Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals

AU - Nielsen, Hans J

AU - Brünner, Nils

AU - Jørgensen, Lars Nannestad

AU - Olsen, Jesper

AU - Rahr, Hans B

AU - Thygesen, Knud

AU - Hoyer, Ute

AU - Laurberg, Søren

AU - Stieber, Petra

AU - Blankenstein, Marinus A

AU - Davis, Gerard

AU - Dowell, Barry L

AU - Christensen, Ib J

AU - NN, NN

AU - Jørgensen, Lars Nannestad

AU - Olsen, Jesper Arnold

PY - 2011/1

Y1 - 2011/1

N2 - Objective. The combination of plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) and carcinoembryonic antigen (CEA) may be valuable biomarkers for early detection of colorectal cancer (CRC). A prospective, population based study was performed to validate this hypothesis. Material and methods. Individuals (n =4509) referred for large bowel endoscopy due to symptoms of CRC were prospectively included. Baseline data and concurrent diseases were recorded. The primary endpoint was detection of CRC and findings at examinations were recorded using International Classification of Diseases-10 codes. Plasma was obtained before endoscopy and TIMP-1 and CEA levels were determined after the inclusion of all individuals. Results. Findings were based on sigmoidoscopy in 1766 and colonoscopy in 2743 individuals. Colon cancer (CC) was detected in 184 and rectal cancer in 110 individuals. Ten individuals with other cancers, 856 with adenomas and 1176 with non-neoplastic findings were also detected. The biomarker levels were increased in a variety of diseases including CRC compared to individuals without any findings at endoscopy. A multivariable analysis demonstrated that both markers were significant and independent detectors of CRC. Combining both biomarkers, independent contributions from each (TIMP-1, odds ratio (OR) =1.8 (95% confidence interval (CI): 1.4-2.2), p < 0.0001; CEA < 5 ng/ml, OR= 1.6, 1.3-1.9, or ≥5 ng/ml, OR =2.3, 95% CI: 1.9-2.7 (p < 0.0001)) were obtained. Subgroup analysis of individuals examined by colonoscopy with CC as the endpoint showed that combining both biomarkers, independent contributions from each (TIMP-1, OR= 2.5, 95% CI: 1.8-3.4, p < 0.0001; CEA < 5 ng/ml, OR =1.4, 95% CI: 1.1-1.8, and CEA ≥ 5 ng/ml, OR= 2.3, 95% CI: 1.8-3.0 (p < 0.0001)) were obtained. Conclusions. This prospective validation study supports the use of the combination of plasma TIMP-1 and CEA protein measurements as a potential aid in early detection of CRC and specifically of CC.

AB - Objective. The combination of plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) and carcinoembryonic antigen (CEA) may be valuable biomarkers for early detection of colorectal cancer (CRC). A prospective, population based study was performed to validate this hypothesis. Material and methods. Individuals (n =4509) referred for large bowel endoscopy due to symptoms of CRC were prospectively included. Baseline data and concurrent diseases were recorded. The primary endpoint was detection of CRC and findings at examinations were recorded using International Classification of Diseases-10 codes. Plasma was obtained before endoscopy and TIMP-1 and CEA levels were determined after the inclusion of all individuals. Results. Findings were based on sigmoidoscopy in 1766 and colonoscopy in 2743 individuals. Colon cancer (CC) was detected in 184 and rectal cancer in 110 individuals. Ten individuals with other cancers, 856 with adenomas and 1176 with non-neoplastic findings were also detected. The biomarker levels were increased in a variety of diseases including CRC compared to individuals without any findings at endoscopy. A multivariable analysis demonstrated that both markers were significant and independent detectors of CRC. Combining both biomarkers, independent contributions from each (TIMP-1, odds ratio (OR) =1.8 (95% confidence interval (CI): 1.4-2.2), p < 0.0001; CEA < 5 ng/ml, OR= 1.6, 1.3-1.9, or ≥5 ng/ml, OR =2.3, 95% CI: 1.9-2.7 (p < 0.0001)) were obtained. Subgroup analysis of individuals examined by colonoscopy with CC as the endpoint showed that combining both biomarkers, independent contributions from each (TIMP-1, OR= 2.5, 95% CI: 1.8-3.4, p < 0.0001; CEA < 5 ng/ml, OR =1.4, 95% CI: 1.1-1.8, and CEA ≥ 5 ng/ml, OR= 2.3, 95% CI: 1.8-3.0 (p < 0.0001)) were obtained. Conclusions. This prospective validation study supports the use of the combination of plasma TIMP-1 and CEA protein measurements as a potential aid in early detection of CRC and specifically of CC.

U2 - 10.3109/00365521.2010.513060

DO - 10.3109/00365521.2010.513060

M3 - Journal article

C2 - 20799911

SN - 0036-5521

VL - 46

SP - 60

EP - 69

JO - Scandinavian Journal of Gastroenterology

JF - Scandinavian Journal of Gastroenterology

IS - 1

ER -

Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals

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