CRC screening: Old science, new application

Xchange newsletter, issue 25 – Summer 2008

Colorectal cancer (CRC) is the third most common cancer in the UK. Approximately one in 20 people in the UK will develop bowel cancer during their lifetime with more than 16,000 people dying from it each year. It is the second leading cause of cancer deaths [1].

Although guaiac-based faecal occult blood testing is inexpensive and has proved to be effective at reducing CRC mortality rates, immunochemical testing is more patient friendly, more convenient and has a similar or better sensitivity and specificity [2].

Faecal occult blood tests

Polyps and bowel cancers in the large intestine sometimes bleed, which is the basis of faecal occult blood (FOB) tests and CRC screening. There are currently two types of FOB tests, guaiac (gFOB) and immunochemical (iFOB), each designed to detect one of the two main components of haemoglobin. While common gFOB tests detect haematin moiety, modern science has developed novel iFOB tests designed to detect the protein part of haemoglobin [2].

gFOB

First used in 1864, gFOB tests consist of a thick piece of paper impregnated with guaiac, from the Guaiacum tree. Patients are asked to smear two samples from each of three consecutive motions onto three pieces of the film. In the lab, a few drops of hydrogen peroxide are added. If haematin is present, its peroxidase-like activity catalyses the reaction causing the test to turn blue within 60 seconds.

False positives can be caused due to a lack of differentiation between human and animal haematin and reactions caused by plant peroxidases (from radishes and broccoli for example). These limitations necessitate pre-test dietary restrictions. Additionally, false negatives may be caused by bad samples, undetectable quantities of blood or the presence of large quantities of vitamin C, which is a reducing agent and negates the effects of haematin.

iFOB

Because haemoglobin molecules consist of four protein haematin entities with species specific amino acid combinations, iFOB tests can detect human globulin specifically and do not require intact haemoglobin for reaction. Pre-test dietary restrictions are therefore unnecessary. iFOB test kits are able to detect much lower levels of blood and require fewer test cards to ensure robust results. Additionally, there is the potential to automate the iFOB testing process.

NHS Bowel Cancer Screening Programme

Combined results from three randomised controlled trials reported in the 1990’s using biennial guaiac screening, showed that participants allocated to screening had a 15% reduction in the relative risk of colorectal cancer mortality [3].  The results of these studies prompted NHS Bowel Cancer Screening Programme pilots in Scotland and England that replicated the results of initial research, leading the Government to roll out a national programme which will achieve nationwide coverage by 2009 [4].

Screening strategy

Abnormal screening results indicate the need for further investigation, usually in the form of a diagnostic colonoscopy. Trials have shown that the benefits of screening include a reduction in colorectal cancer mortality, a possible reduction in cancer incidence through the detection and removal of colorectal adenomas, and potentially, less invasive surgery due to earlier treatment of colorectal cancer [3].

There is a concern that the additional sensitivity of iFOB tests would lead to more false positive results. While trials in large screening populations are currently underway, smaller studies have already shown that the sensitivity and specificity of iFOB tests can be adjusted depending on the threshold set for globin detection. A pilot study in Australia showed that ‘altering the threshold for evaluation of the intensity ratio could preserve the cancer detection rate while lowering false-positive rate’ [2].

Abbott is currently developing an iFOB kit offering the advantages of no dietary restrictions during sample collection, the ability to quantify the cutoff, the need for fewer samples and the potential to automate the test.

Bowel cancer cell

Coloured scanning electron micrograph (SEM) of an intestinal cancer cell. Cancer cells are typically large and they divide rapidly in a chaotic, uncontrolled manner. They may clump to form tumours which invade and destroy surrounding tissues. Cancer of the small intestine is rare, but cancer of the large intestine is one of the most common cancers in the developed world. © Science Photo Library

References

[1] CancerResearch UK, 2005. Cancerstats
[2] Ouyang, D.L., et al., Am. J. Of Gastroentorol, 2005; 100:1393-1403
[3] Cochrane Database of Systematic Reviews, 2006. Screening for colorectal cancer using the
faecal occult blood test: an update.
[4] www.cancerscreening.nhs.uk