title: Increased serological cancer-associated biomarker levels at large bowel endoscopy and risk of subsequent primary cancer (†).
abstract: BACKGROUND
  Frequently, subjects offered colonoscopy due to symptoms of colorectal neoplasia are diagnosed with diverticula. The symptoms may, however, also be related to extra-colonic neoplasia. The present retrospective study evaluated a possible association between increased levels of predefined biomarkers in subjects diagnosed with diverticula and risk of developing a primary malignant disease.
  
  
  METHODS
  During 2004/2005, about 4509 subjects were included in a multicenter study with collection of blood samples before bowel endoscopy. The aim was to evaluate a relation between the protein biomarkers CEA, TIMP-1, CA19-9 and YKL-40 and findings at endoscopy. Diverticula were diagnosed in 1021 subjects. By 31 December 2012, subjects who had developed primary malignancy were identified retrospectively and relation between biomarker levels at endoscopy and risk of developing primary malignancy was calculated. The relation with the four biomarkers was divided into three groups: 0 = none increased; 1 = one increased and 2 = two or more increased.
  
  
  RESULTS
  In the observation period, 148 subjects developed a primary malignant disease. Univariable analyzes of the biomarker levels showed that CEA, TIMP-1 and CA19-9 were significantly associated with development of primary malignancy. A multivariable analysis showed that increased levels were associated with development of malignancy (p < 0.0001). The 1- and 5-year cumulative risks of being diagnosed with a primary malignancy were: group 0: 1.1%/5.5%; group 1: 4.2%/10.1% and group 2: 11.4%/18.8%, respectively.
  
  
  CONCLUSIONS
  Increased levels of CEA, TIMP-1 and CA19-9 at endoscopy with findings of diverticula were associated with a significantly increased risk of being diagnosed with a subsequent primary malignant disease.
authors.affiliation: a Department of Surgical Gastroenterology , Hvidovre Hospital , Hvidovre , Denmark ;
authors.forename: Martin H
authors.initials: MH
authors.lastname: Hvolris
authors.affiliation: a Department of Surgical Gastroenterology , Hvidovre Hospital , Hvidovre , Denmark ;
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Piper
authors.affiliation: a Department of Surgical Gastroenterology , Hvidovre Hospital , Hvidovre , Denmark ;
authors.forename: Emilie
authors.initials: E
authors.lastname: Hammer
authors.affiliation: b Department of Surgical Gastroenterology , Bispebjerg Hospital , Bispebjerg , Denmark ;
authors.forename: Lars N
authors.initials: LN
authors.lastname: Jørgensen
authors.affiliation: c Department of Surgical Gastroenterology , Glostrup Hospital , Glostrup , Denmark ;
authors.forename: Jesper
authors.initials: J
authors.lastname: Olsen
authors.affiliation: d Department of Surgical Gastroenterology , Odense University Hospital , Odense , Denmark ;
authors.forename: Hans B
authors.initials: HB
authors.lastname: Rahr
authors.affiliation: e Department of Surgery , Randers Hospital , Randers , Denmark ;
authors.forename: Knud T
authors.initials: KT
authors.lastname: Nielsen
authors.affiliation: f Department of Surgical Gastroenterology , Aarhus University Hospital , Aarhus , Denmark ;
authors.forename: Søren
authors.initials: S
authors.lastname: Laurberg
authors.affiliation: a Department of Surgical Gastroenterology , Hvidovre Hospital , Hvidovre , Denmark ;
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: g Institute of Veterinary Disease Biology, University of Copenhagen , Frederiksberg , Denmark ;
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.affiliation: h Department of Oncology , Herlev Hospital , Herlev , Denmark ;
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.affiliation: i Abbott Laboratories Inc, Cancer Core R&D , Abbott Park , IL , USA ;
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Davis
authors.affiliation: i Abbott Laboratories Inc, Cancer Core R&D , Abbott Park , IL , USA ;
authors.forename: Barry L
authors.initials: BL
authors.lastname: Dowell
authors.affiliation: a Department of Surgical Gastroenterology , Hvidovre Hospital , Hvidovre , Denmark ;|j Institute of Clinical Medicine, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D000071451:Chitinase-3-Like Protein 1 / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D004241:Diverticulum, Colon / Q000175:diagnosis*; D016099:Endoscopy, Gastrointestinal; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D019715:Tissue Inhibitor of Metalloproteinase-1; C578959:carbohydrate antigen 199, human
keywords: CA19-9; CEA; TIMP-1; YKL-40; colorectal cancer; diverticula; endoscopy; malignancy