Blood-based biomarkers at large bowel endoscopy and prediction of future malignancies

Thomas S. Kring, Thomas B. Piper, Lars Nannestad Jørgensen, Jesper Olsen, Hans B. Rahr, Knud T. Nielsen, Søren Laurberg, Gerard Davis, Barry Dowell, Julia Sidenius Johansen, Ib Jarle Christensen, Nils Brünner, Hans J. Nielsen

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Abstract

Soluble cancer-related protein biomarker levels may be increased in subjects without findings at large bowel endoscopy performed due to symptoms associated with colorectal cancer. The present study focused on a possible association between increased biomarker levels in such subjects and subsequent development of malignant diseases. In a major study of 4,990 subjects undergoing large bowel endoscopy, 691 were without pathology and comorbidity. Plasma levels of TIMP-1, CEA, CA19-9, and YKL-40 were determined in samples collected just before endoscopy and compared with subsequent development of a malignant disease within a period of 7-8 years. The upper 90% limits of the reference levels of every single protein were used to differentiate between normal and increased levels. The levels were separated into three groups: 0, none of the biomarkers increased; 1, one biomarker increased; 2, two or more biomarkers increased. A total of 43 subjects developed a primary malignant disease in the observation period. Univariatly, increase of all four biomarkers was significantly associated with subsequent development of a malignant disease. A multivariate analysis showed that increased biomarker levels were associated with subsequent development of a malignant disease (P = 0.002). The cumulative risk of developing malignant disease within the first 5 years after endoscopy was group 0, 3.3%; group 1, 5.8%; group 2, 7.8%. It is concluded that increased levels of plasma TIMP-1, CEA, CA19-9, and serum YKL-40 at large bowel endoscopy without findings may be associated with an increased risk of developing a subsequent malignant disease.

OriginalsprogEngelsk
TidsskriftBiomarkers in Cancer
Vol/bind7
Sider (fra-til)57-61
Antal sider5
ISSN1179-299X
DOI
StatusUdgivet - 2015

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