title: Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples.
abstract: BACKGROUND
  Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim of this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 for the early detection of CRC in an asymptomatic cohort.
  
  
  METHODS
  This nested case-control study within UKCTOCS used 381 serial serum samples from 40 women subsequently diagnosed with CRC, 20 women subsequently diagnosed with benign disease and 40 matched non-cancer controls with three to four samples per subject taken annually up to 4 years before diagnosis. CEA, CYFRA21-1 and CA125 were measured using validated assays and performance of markers evaluated for different pre-diagnosis time groups.
  
  
  RESULTS
  CEA levels increased towards diagnosis in a third of all cases (half of late-stage cases), whereas longitudinal profiles were static in both benign and non-cancer controls. At a threshold of >5 ng ml(-1) the sensitivities for detecting CRC up to 1 and 4 years before clinical presentation were 25% and 13%, respectively, at 95% specificity. At a threshold of >2.5 ng ml(-1), sensitivities were 57.5% and 38.4%, respectively, with specificities of 81% and 83.5%. CYFRA21-1 and CA125 had no utility as screening markers and did not enhance CEA performance when used in combination. CEA gave average lead times of 17-24 months for test-positive cases.
  
  
  CONCLUSIONS
  CEA is elevated in a significant proportion of individuals with preclinical CRC, but would not be useful alone as a screening tool. This work sets a baseline from which to develop panels of biomarkers which combine CEA for improved early detection of CRC.
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: D S
authors.initials: DS
authors.lastname: Thomas
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: E-O
authors.initials: EO
authors.lastname: Fourkala
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: S
authors.initials: S
authors.lastname: Apostolidou
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Gunu
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: A
authors.initials: A
authors.lastname: Ryan
authors.affiliation: 1] Women's Cancer, Institute for Women's Health, University College London, Gower Street, London WC1E 6BT, UK [2] Faculty of Medical and Human Sciences, 1.018 Core Technology Facility, University of Manchester, Grafton Street Manchester M13 9NT, UK.
authors.forename: I
authors.initials: I
authors.lastname: Jacobs
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: U
authors.initials: U
authors.lastname: Menon
authors.affiliation: Abcodia Ltd, The Network Building, 97 Tottenham Court Road, London W1T 4TP, UK.
authors.forename: W
authors.initials: W
authors.lastname: Alderton
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: A
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.affiliation: Women's Cancer, Institute for Women's Health, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: J F
authors.initials: JF
authors.lastname: Timms
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D053539:Keratin-19 / Q000097:blood*; D008137:Longitudinal Studies; D008875:Middle Aged
chemical_list: D000951:Antigens, Neoplasm; D018394:CA-125 Antigen; D002272:Carcinoembryonic Antigen; D053539:Keratin-19; C102012:antigen CYFRA21.1