Skip to main content
SpringerLink
Log in

Molecular approaches to stool screening for colorectal cancer

  • Published:
Current Colorectal Cancer Reports

Abstract

Detection of molecular markers of colorectal neoplasia in feces provides innovative, noninvasive means to screen for colorectal cancer and adenomas. Molecular markers, de.ned as a specific molecule or molecular structure, reach the gut lumen by the processes of leakage, secretion, cell exfoliation, or a combination of these processes. Exfoliated cells are the most likely to be specific for neoplasia. Fecal molecular markers will serve as the noninvasive first test in two-step screening for colorectal cancer, in which the second test is colonoscopy. This first step separates people into two categories: those more likely to have neoplasia and those less likely. Any new test should therefore be an improvement over the proven, but only modestly effective, guaiac-based fecal occult blood tests. The leakage marker hemoglobin can now be accurately detected by fecal immunochemical tests (FIT) for hemoglobin. These tests perform better than guaiac tests in specificity, sensitivity, and subject participation. Secreted mucins have inadequate specificity. Multitarget fecal DNA tests for exfoliated cells have not achieved their potential and have not been shown to be an improvement over FIT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Young GP, Allison J: Screening for colorectal cancer. In Textbook of Gastroenterology, edn 5. Edited by Yamada T, Alpers D, Kaplowitz N, et al.: Philadelphia: Lippincott Williams & Wilkins; 2006:in press.

    Google Scholar 

  2. Ouyang DL, Chen JJ, Getzenberg RH, Schoen RE: Noninvasive testing for colorectal cancer: a review. Am J Gastroenterol 2005, 100:1393–1403. Thorough review of noninvasive screening tests from the US perspective. Clearly supports a role for such tests.

    Article  PubMed  CAS  Google Scholar 

  3. Morrison AS: Screening. In Modern Epidemiology. Edited by Rothman KJ, Greenland S. Philadelphia: Lippincott-Raven; 1998:499–518.

    Google Scholar 

  4. Osborn NK, Ahlquist DA: Stool screening for colorectal cancer: molecular approaches [review]. Gastroenterology 2005, 128:192–206. Excellent review of the molecular tests from the perspectives of applied biology and technology.

    Article  PubMed  CAS  Google Scholar 

  5. Young GP, St John DJ, Winawer SJ, et al.: Choice of fecal occult blood tests for colorectal cancer screening: recommendations based on performance characteristics in population studies. Am J Gastroenterol 2002, 97:2499–2507. An evidence-based analysis of papers in which FIT and GFOBT have been directly compared. The paper takes an international approach and details how the different tests are relevant to the different settings.

    PubMed  Google Scholar 

  6. Woolf SH: A smarter strategy? Reflections on fecal DNA screening for colorectal cancer. N Engl J Med 2004, 351:2755–2758. Critique of screening for colorectal cancer based on fecal DNA testing with particular emphasis on the broader processes of screening and how these are critical to achieving the best outcomes.

    Article  PubMed  CAS  Google Scholar 

  7. Allison JE: Screening for colorectal cancer 2003: Is there still a role for the FOBT? Tech Gastrointest Endosc 2003, 5:127–133.

    Article  Google Scholar 

  8. Woolf SH: The best screening test for colorectal cancer - a personal choice. N Engl J Med 2000, 343:1641–1643.

    Article  PubMed  CAS  Google Scholar 

  9. Fletcher RH: Screening colonoscopy: Option or preference? Gastrointest Endosc 2000, 51:624–627.

    Article  PubMed  CAS  Google Scholar 

  10. Ransohoff DF, Lang CA: Sigmoidoscopic screening in the 1990s. JAMA 1993, 269:1278–1281.

    Article  PubMed  CAS  Google Scholar 

  11. Smith RA, Cokkinides V, Eyre HJ: American Cancer Society guidelines for the early detection of cancer, 2003. CA Cancer J Clin 2003, 53:27–43.

    PubMed  Google Scholar 

  12. Launoy GD, Bertrand HJ, Berchi C, et al.: Evaluation of an immunochemical fecal occult blood test with automated reading in screening for colorectal cancer in a general average-risk population. Int J Cancer 2005, 115:493–496. Clear demonstration of how a quantitative FIT can be used to provide flexibility with screening parameters. It is possible to choose a fecal hemoglobin level that gives either better sensitivity or better specificity, depending on preference.

    Article  PubMed  CAS  Google Scholar 

  13. Wong BC, Wong WM, Cheung KL, et al.: A sensitive guaiac faecal occult blood test is less useful than an immunochemical test for colorectal cancer screening in a Chinese population. Aliment Pharmacol Ther 2003, 18:941–946.

    Article  PubMed  Google Scholar 

  14. Hughes K, Leggett B, Del Mar C, et al.: Guaiac versus immunochemical tests: faecal occult blood test screening for colorectal cancer in a rural community. Aust N Z J Public Health 2005, 29:358–364.

    PubMed  Google Scholar 

  15. Cole SR, Young GP, Esterman A, et al.: A randomised trial of the impact of new faecal haemoglobin test technologies on population participation in screening for colorectal cancer. J Med Screen 2003, 10:117–122. Randomized controlled trial of the impact of new technologies inherent in FIT compared with GFOBT, and how this improves population acceptance of screening.

    Article  PubMed  CAS  Google Scholar 

  16. Smith A, Cole S, Morcom J, et al.: Colorectal cancer screening: direct comparison of a brush-sampling faecal immunochemical test for haemoglobin with a guaiac FOBT. J Gastroenterol Hepatol 2003, 18:B24.

    Google Scholar 

  17. Young GP, St John DJ, Cole SR, et al.: Prescreening evaluation of a brush-based faecal immunochemical test for haemoglobin. J Med Screen 2003, 10:123–128.

    Article  PubMed  CAS  Google Scholar 

  18. Castiglione G, Grazzini G, Miccinesi G, et al.: Basic variables at different positivity thresholds of a quantitative immunochemical test for faecal occult blood. J Med Screen 2002, 9:99–103.

    Article  PubMed  CAS  Google Scholar 

  19. Kronborg O, Ugstad M, Fuglerud P, et al.: Faecal calprotectin levels in a high risk population for colorectal neoplasia. Gut 2000, 46:795–800.

    Article  PubMed  CAS  Google Scholar 

  20. Vironen J, Kellokumpu S, Andersson LC, Kellokumpu I: Comparison of a peanut agglutinin test and an immunochemical faecal occult blood test in detecting colorectal neoplasia in symptomatic patients. Scand J Clin Lab Invest 2004, 64:140–145.

    Article  PubMed  CAS  Google Scholar 

  21. Nair P, Lagerholm S, Dutta S, et al.: Coprocytobiology: on the nature of cellular elements from stools in the pathophysiology of colonic disease. J Clin Gastroenterol 2003, 36:S84-S96.

    Article  PubMed  Google Scholar 

  22. Stremmel C, Wein A, Hohenberger W, Reingruber B: DNA microarrays: a new diagnostic tool. Int J Colorect Dis 2002, 17:131–136.

    Article  CAS  Google Scholar 

  23. Klaassen CH, Jeunink MA, Prinsen CF, et al.: Quantification of human DNA in feces as a diagnostic test for the presence of colorectal cancer. Clin Chem 2003, 49:1185–1187.

    Article  PubMed  CAS  Google Scholar 

  24. Tagore K, Lawson M, Yucaitis J, et al.: Sensitivity and specificity of a stool DNA multitarget DNA assay panel for the detection of advanced colorectal neoplasia. Clin Colorectal Cancer 2003, 3:47–53.

    Article  PubMed  CAS  Google Scholar 

  25. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al.: Fecal DNA versus fecal occult blood for colorectal cancer screening in an average-risk population. N Engl J Med 2004, 351:2704–2714. The best and most recent paper on the application of fecal DNA testing in screening. Note the critiques elsewhere (references 26 and 6) concerning conclusions and design.

    Article  PubMed  CAS  Google Scholar 

  26. Young GP, Worthley DL: Screening with a fecal multitarget DNA test. Gastroenterology 2005, 129:757–759. Commentary on the role of and prospects for screening by fecal DNA test. Critique on the design of the Imperiale paper [25], especially in relation to comparison with the earliest guaiac-based FOBT (Hemoccult).

    Article  PubMed  Google Scholar 

  27. Koshiji M, Yonekura Y, Saito T, Yoshioka K: Microsatellite analysis of fecal DNA for colorectal cancer detection. J Surg Oncol 2002, 80:34–40.

    Article  PubMed  CAS  Google Scholar 

  28. Muller HM, Oberwalder M, Fiegl H, et al.: Methylation changes in faecal DNA: a marker for colorectal cancer screening? Lancet 2004, 363:1283–1285.

    Article  PubMed  CAS  Google Scholar 

  29. Davidson LA, Lupton JR, Miskovsky E, et al.: Quantification of human intestinal gene expression profiles using exfoliated colonocytes: a pilot study. Biomarkers 2003, 8:51–61.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Flinders University, Bedford Park, 5042, Adelaide, South Australia, Australia

    Graeme P. Young MD, FRACP

Authors
  1. Graeme P. Young MD, FRACP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Graeme P. Young MD, FRACP.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Young, G.P. Molecular approaches to stool screening for colorectal cancer. Curr colorectal cancer rep 2, 30–35 (2006). https://doi.org/10.1007/s11888-006-0015-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11888-006-0015-x

Keywords

Search

Navigation