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  • Review Article
  • Published:

Colorectal cancer screening: prospects for molecular stool analysis

Nature Reviews Cancer volume 5, pages 199–209 (2005)Cite this article

Key Points

  • Colorectal cancer (CRC) is amenable to screening: it has a recognizable early stage and a defined natural history; surgical treatment of malignancy is effective; and pre-malignant lesions can be removed if detected. However, it is not yet clear whether screening should target early cancers or pre-malignant adenomas.

  • Current screening tests either detect the presence of blood in stool (faecal occult blood testing) or identify gross abnormalities (for example, flexible sigmoidoscopy and colonoscopy). All current tests are limited in patient acceptability and/or effectiveness.

  • There are prospects for new screening tests based on increased understanding of the biology and natural history of CRC. There is considerable interest in stool testing, which is non-invasive; does not require bowel preparation; potentially enables screening of the entire length of the colon and rectum; and produces specimens that are transportable.

  • One category of stool test involves detecting cells or cell contents in stool, for which colonocytes are likely to be a better target than blood. Biomarkers such as minichromosome maintenance proteins could indicate the presence of CRC cells in stool and/or facilitate the identification of such cells following colonocyte isolation.

  • An alternative approach involves testing for abnormal DNA in stool, using target genes identified as being abnormal in the colorectal adenoma–carcinoma sequence. Individual DNA tests generally have high specificity but low sensitivity, so multitarget DNA assays have been developed.

  • Large-scale evaluation of candidate tests, either singly or in combination, is now required. Of particular value would be randomized controlled trials showing a reduction in CRC incidence and/or mortality in the tested individuals.

  • An effective screening strategy would produce extra health-care provision costs, although these would be balanced by a reduced requirement to treat patients with established CRC. 'Halo effects' of an effective screening test would produce benefits for patients with symptomatic CRC as well as the screened population.

Abstract

Colorectal cancer is common. As many patients present with advanced disease, an effective screening test would have substantial clinical benefits. Recent progress in understanding the biology of colorectal cancer (and of cancer cells in general) has led to possible new approaches to screening. In particular, there are prospects of developing tests based on analysis of stool, which promise improved accuracy, safety, affordability and patient compliance.

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Figure 1: The site distribution of colorectal cancer in England and Wales between 1971 and 1994.
Figure 2: The colorectal adenoma–carcinoma sequence.

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Author information

Authors and Affiliations

  1. Medical Research Council Cancer Cell Unit, Hutchison/MRC Research Centre, Hills Road, Cambridge, CB2 2XZ, UK

    R. Justin Davies & Nicholas Coleman

  2. Department of General Surgery, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    R. Justin Davies & Richard Miller

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Correspondence to Nicholas Coleman.

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Nicholas Coleman is entitled to a share of royalties received by Cancer Research Technology Ltd on sales of products related to the use of MCM detection in cancer diagnosis.

Related links

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DATABASES

Entrez Gene

APC

BRAF

CDKN2A

KRAS

MGMT

MLH1

MSH2

MSH3

MSH6

MYC

PMS1

PMS2

SFRP2

SMAD2

SMAD4

TP53

National Cancer Institute

colorectal cancer

OMIM

familial adenomatous polyposis

hereditary non-polyposis colorectal cancer

FURTHER INFORMATION

American Cancer Society

Cancer Research and Prevention Foundation

Colon Cancer Concern

English Colorectal Cancer Screening Pilot

Exact Sciences web page on PreGen-Plus

Exact Sciences

NCI study on the detection of colorectal cancer

Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

UK National Screening Committee

Glossary

FLEXIBLE SIGMOIDOSCOPE

A flexible fibre-optic instrument inserted through the anus, which enables direct visual examination of the lining of the rectum and distal colon.

SPECIFICITY

The likelihood that a test is negative in the absence of disease.

CASE–CONTROL STUDY

A study in which patients who already have a certain condition are compared with people who do not.

COHORT STUDY

A study in which patients who have a certain condition and/or receive a particular test or treatment are followed over time and compared with another group of patients who are not subject to the condition or intervention.

SENSITIVITY

The likelihood that a test is positive in the presence of disease.

COMPUTER TOMOGRAPHY

A diagnostic imaging technique that uses specialized X-ray equipment to obtain image data from different angles, followed by computer processing of the information to show a cross-section of tissues and organs.

GUAIAC TEST

Faecal occult blood test cards are impregnated with guaiac resin, obtained from the wood of Guaiacum officinale trees (which are native to central America and the Carribean). The cards are developed with a liquid hydrogen-peroxide solution that causes the guaiac to turn blue in the presence of the peroxidase-like enzymatic activity of haemoglobin.

DIVERTICULAR DISEASE

A condition in which pouches of mucosa and submucosa protrude through the wall of the colon, with the risk of mucosal ulceration and haemorrhage.

ENZYME-LINKED IMMUNOSORBENT ASSAY

An assay for immunological detection and quantitation of single or multiple antigens or antibodies in a biological sample.

ENTEROPATHY

Disease of the intestinal tract.

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

Prostaglandin inhibitors with anti-inflammatory and analgesic properties.

HUMAN EPITHELIAL ANTIGEN

An adhesion molecule, also known as Ep-CAM, that is broadly expressed by (and specific to) normal and neoplastic epithelial cells.

LIQUID-PHASE ASSAY

An assay carried out in solution, rather than on a solid support.

TELOMERASE

A ribonucleoprotein enzyme complex that stabilizes the length of chromosome telomeric ends by adding hexameric nucleotide repeats.

TELOMERIC REPEAT AMPLIFICATION PROTOCOL

A sensitive assay for measuring telomerase activity, in which telomerase products are generated and subsequently amplified by PCR.

DECAY-ACCELERATING FACTOR

An intrinsic cell membrane inhibitor of autologous complement attack.

SANDWICH ELISA

An ELISA variant in which antigen is captured between two layers of antibodies.

CARCINOEMBRYONIC ANTIGEN

An immunoglobulin supergene family glycoprotein that is normally only present during fetal development, but can be re-expressed by certain malignancies, including colorectal cancer.

SINGLE-STRAND CONFORMATION POLYMORPHISM

A method for detecting single base changes in genes, based on differences in the secondary structure of single-stranded DNA molecules causing an alteration of mobility in non-denaturing gel electrophoresis.

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Davies, R., Miller, R. & Coleman, N. Colorectal cancer screening: prospects for molecular stool analysis. Nat Rev Cancer 5, 199–209 (2005). https://doi.org/10.1038/nrc1569

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