Colon cancer cells

Genetic testing for colorectal cancer

25/3/06. By Chrissie Giles. Reviewed by Jules Harvey and Robin Phillips

A variety of tests, both genetic and non-genetic, can be used to predict and diagnose colorectal cancer.

Non-genetic predictive testing

Looking at a patient's family history can help identify people at risk from developing colorectal cancer. Members of families with a history of familial adenomatous polyposis (FAP) or hereditary non-polyposis colorectal cancer (HNPCC) - hereditary colorectal cancer syndromes - can be genetically screened for the relevant mutations (i.e. the ones affecting their family) if they are known (see predictive genetic testing ).

For patients with a 'moderate' family history (i.e. one first-degree relative with colorectal cancer diagnosed before the age of 45), the relative risk of developing colorectal cancer is 1.7 times that in a person without a family history. Colonoscopy (investigation of the colon with a small camera) is an invasive procedure, time consuming and expensive. Although it is recommended for patients with known HNPCC or FAP mutations, patients with a moderate family history are not routinely offered this treatment. Instead, regular faecal occult blood tests (FOBTs) – used to detect blood in the faeces, since colorectal cancers tend to bleed – are recommended, with colonoscopy only if the FOBT is positive. FOBT is quick, simple and effective in catching colorectal cancer early.

At the end of 2004, the then Health Secretary John Reid announced that a nationwide screening programme using FOBT will be introduced in April 2006 for men and women in their 60s. Large-scale pilots involving flexible sigmoidoscopy (FSIG) (examination of the sigmoid colon with a small camera) for people in their 50s were also announced.

However, like all clinical tests, FOBT is not perfect. Because it detects blood in the faeces (stool), non-cancerous conditions like haemorrhoids (piles) and Crohn's disease can cause a false positive result. Diet can also cause a false positive result and so all positive tests require further evaluation by colonoscopy or sigmoidoscopy and barium enema.

Research is underway to see if molecular stool testing - for chemicals released by colorectal cancers - can make the test more specific (fewer false positives, positive result only for colorectal cancer patients) and more sensitive (fewer colorectal cancers missed). Molecular stool tests might also be useful for monitoring colorectal cancer patients in remission for signs of cancer recurrence.

Predictive genetic testing

Genetic tests for familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC) have been developed. These detect mutations in the APC and MMR genes (MSH2 and MLH1) respectively.

In patients with FAP, current tests are able to detect APC mutations in about 85 per cent of cases. The other 15 per cent may have unrecognised mutations or mutations in one or more other genes. more on FAP .

In HNPCC, again, about 85 per cent of mutations are recognised in affected people. To improve the detection, microsatellite instability can be looked for in tumour samples before they are tested for HNPCC mutations. Testing for HNPCC is further complicated due to the fact that there are over 200 different mutations associated with the disease. More on HNPCC and microsatellite instability .

If an individual's genetic tests prove positive, then family members are offered regular colonoscopy.

Diagnostic genetic testing

As well as predicting whether someone has FAP or HNPCC, genetic tests can sometimes help doctors in the diagnosis of sporadic colorectal cancer (e.g. young patients).

Although not routinely tested for in the UK, specific mutations have been shown to relate to the response of the cancer to particular drug treatments and also the prognosis of the tumour. For example, tumours with defective MMR genes often respond to different drug therapies to those without. This raises exciting possibilities for the future.

Genetic screening

Although genetic screening can identify most patients with FAP or HNPCC, over 90 per cent of patients with CRC do not have inherited mutations in any of the known susceptibility genes. As a result, there are no plans for population-wide screening.

In late 2004, the Human Fertilisation and Embryology Authority (HFEA) approved the screening of embryos for FAP. University College London (UCL) has been licensed by the HFEA to perform pre-implantation genetic diagnosis, where the embryos of parents affected by FAP can be tested for specific FAP mutations. Any embryos found to be carrying the FAP mutation are then not re-implanted during the in-vitro fertilisation process. This procedure might prevent some cases of FAP from occurring, but is controversial and has also fuelled the 'designer baby' debate. For more details see HEFA news article .


Cancer Research UK: About Cancer

CancerBACUP: Cancer of the large bowel

Beating Bowel Cancer

Image credit: Annie Cavanagh. Colour-enhanced image of human colon cancer cells in culture.

Share |
Icon representing the Cancer file section.
Wellcome Trust, Gibbs Building, 215 Euston Road, London NW1 2BE, UK T:+44 (0)20 7611 8888