title: Blood-based Biomarkers at Large Bowel Endoscopy and Prediction of Future Malignancies.
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.
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kring
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Piper
authors.affiliation: Digestive Disease Center, Bispebjerg Hospital, Copenhagen, Denmark. ; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lars N
authors.initials: LN
authors.lastname: Jørgensen
authors.affiliation: Department of Surgical Gastroenterology, Glostrup Hospital, Glostrup, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Olsen
authors.affiliation: Department of Surgical Gastroenterology, Odense University Hospital, Odense, Denmark.
authors.forename: Hans B
authors.initials: HB
authors.lastname: Rahr
authors.affiliation: Department of Surgery, Randers Hospital, Randers, Denmark.
authors.forename: Knud T
authors.initials: KT
authors.lastname: Nielsen
authors.affiliation: Department of Surgical Gastroenterology, Aarhus Hospital THG, Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Laurberg
authors.affiliation: Abbott Diagnostics Division R&D, Chicago, USA.
authors.forename: Gerard
authors.initials: G
authors.lastname: Davis
authors.affiliation: Abbott Diagnostics Division R&D, Chicago, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Dowell
authors.affiliation: Department of Oncology, Herlev Hospital, Herlev, Denmark.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark.
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: Institute of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark. ; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
keywords: CA19-9; CEA; TIMP-1; YKL-40; cancer risk; colorectal cancer; endoscopy