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.
  
  
  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.
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark. h.j.nielsen@ofir.dk
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.forename: Lars N
authors.initials: LN
authors.lastname: Jorgensen
authors.forename: Jesper
authors.initials: J
authors.lastname: Olsen
authors.forename: Hans B
authors.initials: HB
authors.lastname: Rahr
authors.forename: Knud
authors.initials: K
authors.lastname: Thygesen
authors.forename: Ute
authors.initials: U
authors.lastname: Hoyer
authors.forename: Søren
authors.initials: S
authors.lastname: Laurberg
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: Gerard
authors.initials: G
authors.lastname: Davis
authors.forename: Barry L
authors.initials: BL
authors.lastname: Dowell
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002272:Carcinoembryonic Antigen; D019715:Tissue Inhibitor of Metalloproteinase-1