Genetic conditions series
National Genetics and Genomics
Education Centre
Predisposition to
Inherited Bowel Cancer
Facts about Inherited Bowel Cancer
• Bowel cancer is the third most common cancer in the UK. About 1 in 20 people develop bowel
cancer during their lifetime. Most bowel cancer occurs at an older age.
• The majority of bowel cancer is not due to an inherited condition but it is important to
recognise the ~ 5% of bowel cancer associated with an inherited cause.
• Two autosomal dominant conditions with an inherited predisposition are known as Lynch
syndrome (previously called HNPCC) and familial adenomatous polyposis (FAP).
• Individuals with Lynch syndrome have a significantly increased risk of developing bowel
cancer during their lifetime and benefit from additional surveillance, which can reduce
cancer risk by at least two thirds.
• Familial adenomatous polyposis (FAP) is a genetic condition that leads to the development
of many (>100) colonic polyps which need surveillance as at least one may develop into
cancer over time.
Clinical features
Most bowel cancer occurs due to chance. Around 5% of bowel cancer occurs due to an inherited predisposition (inherited or
familial bowel cancer) and clues that may suggest an inherited predisposition to bowel cancer include:
• several individuals on one side of the family who have had bowel cancer
• bowel cancer being diagnosed at a younger age than is usual (below the age of 50)
• a history of bowel and other cancers (particularly endometrial, ovarian, stomach or urinary tract cancer) occurring in the
same individual or in relatives
• an individual who has had multiple colonic polyps (people with Lynch syndrome develop polyps but large numbers
would suggest a diagnosis of familial adenomatous polyposis (FAP).
Tests on cancer tissue from someone in the family may also sometimes suggest an inherited predisposition.
Identifying families with a predisposition to bowel cancer
Individuals may seek information about an inherited predisposition either because they have been affected with bowel
cancer themselves or because they have a family history of bowel cancer.
A family history will first be taken by their bowel cancer team or by their GP. If the family history meets NICE criteria then
a referral should be made to the local genetics department or family history clinic. Most Regional Genetic Centres publish
guidelines on their website for referrals based on information from a family history.
The genetic services will carry out a detailed assessment to estimate an individual’s probability of developing bowel
cancer and also assess the likelihood that there may be a gene alteration associated with the bowel cancer in the family.
Depending on the assessment, there may be recommendations about additional screening and/or genetic testing may be
offered.
Genetic basis
Lynch syndrome
People with the genetic alteration for Lynch syndrome have a higher risk of developing certain types of cancer especially
bowel cancer and endometrial cancer. The lifetime risk of bowel cancer for people with Lynch syndrome is 50- 80%.
This sheet may be photocopied for non-commercial education purposes for healthcare staff
© 2012 NHS National Genetics Education and Development Centre (03/13)
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk
National Genetics and Genomics
Education Centre
Lynch syndrome is caused by an alteration in a type of gene known as a ‘mismatch repair’ gene and is inherited in an
autosomal dominant manner. This means that an affected individual has one usual copy of the gene and one altered copy.
Each child of someone with a gene alteration in one of a pair of mismatch repair genes has a 50% (1 in 2) chance of inheriting
the usual gene and a 50% chance of inheriting the altered gene.
Mismatch repair genes are involved in correcting errors which occur in DNA when DNA is copied. When changes in DNA are
not repaired, they can lead to cancer.
Familial adenomatous polyposis (FAP)
FAP is a separate condition. When the family history gives an autosomal dominant pattern, the condition is most usually
caused by alterations to the APC gene. There can be hundreds of polyps at a young age, with an inevitability that at least
one will become cancerous.
There is another form of FAP (called MUTYH-associated polyposis). It is associated with fewer polyps at an older age than is
typical in FAP but surveillance colonoscopy is warranted because of the high rise of cancer developing. This form is inherited
as an autosomal recessive condition and is due to alterations in both copies of the MUTYH gene.
Clinical management
Individuals identified to be at increased risk of bowel cancer because of their family history, may be offered additional bowel
screening by colonoscopy to detect cancers at an early stage. In families with Lynch syndrome regular colonoscopy may be
offered from the age of 25, and in FAP from age 12 (following genetic testing aged 10) with the aim of determining the best
time to offer prophylactic colectomy.
It is also important that individuals are aware of the possible symptoms of bowel cancer such as change in bowel habit and
to report if these occur between planned colonoscopies.
Evidence is increasing that taking aspirin may reduce the risk of developing bowel cancer. There are currently research
studies looking into how this may benefit people with Lynch syndrome and FAP.
The importance of genetic testing
If a gene alteration is identified in an affected family member then relatives without symptoms can be offered testing to
see whether they have inherited the same gene alteration, and surveillance begun. This use of genetic testing is known as
predictive testing.
Lynch syndrome
Genetic testing can be offered to a person in whom a diagnosis of Lynch syndrome is suspected. There are 4 genes
associated with Lynch syndrome that are currently tested: MLH1, MSH2, MSH6, and PMS2.
Familial adenomatous polyposis
The APC gene (on chromosome 5) is usually tested first in people with or who are suspected of having FAP. Testing for
changes in the MUTYH gene is also available.
References
NHS National Institute for Health and Clinical Excellence Colorectal cancer: the diagnosis and management of colorectal
cancer NICE Clinical guideline 131 http://guidance.nice.org.uk/cg131
The British Society for Human Genetics Directory of UK Genetics Centres
http://www.bshg.org.uk/genetic_centres/uk_genetic_centres.htm
This information is intended for educational use and was current in March 2013. For clinical management it is recommended that local guidelines and
protocol are used.
This sheet may be photocopied for non-commercial education purposes for healthcare staff
© 2012 NHS National Genetics Education and Development Centre (03/13)
Genetics and genomics for healthcare
www.geneticseducation.nhs.uk