Conditions which cause inherited bowel cancer

Lynch syndrome (LS): Lynch syndrome is the most common hereditary bowel cancer syndrome and is the cause of approximately 2–3% of all bowel cancer. It is caused by a pathogenic variant in MLH1, MSH2, MSH6, PMS2, EPCAM or possibly MSH3

It has been estimated that in Europe approximately one million people have LS. Cancers which can be increased in Lynch syndrome include: bowel, womb,  stomach, ovarian, pancreatic, prostate, urinary tract, liver, kidney and bile duct.

If someone has LS, regular bowel screening with colonoscopy is vital and other risk-reducing strategies will be considered. These strategies include detecting and treating an infection called Helicobacter Pylori as well as taking aspirin, and consideration of risk-reducing surgery.

NICE recommends that all womb and bowel cancer should be screened for Lynch syndrome using either immunohistochemistry (IHC) or microsatellite instability (MSI) testing on the tumour. A further test known as MLH1 methylation or BRAF may also be needed. If the tumour testing screens positive, then further testing on a blood/saliva sample is recommended. NHS hospitals are gradually rolling out these recommendations and therefore these tests may be performed on your/or your relative’s tumour.

Familial Adenomatous Polyposis (FAP) and Attenuated Familial Adenomatous Polyposis (AFAP): FAP and AFAP are inherited conditions which cause multiple  bowel polyps (over 100 in classical FAP), as well as a significantly increased risk of bowel, small bowel and other cancers. These conditions are rare: approximately 2-3 people in 100 000 will have FAP. However, about 25% of people with FAP will have a new mutation in the APC gene: this means that it occurred for the first time in them and so they usually won’t have a family history of cancer. If someone has FAP, screening can begin in their teens and they usually consider having their bowel and rectum removed.  AFAP seems to be milder with people having fewer polyps and usually a later age of onset and would need increased bowel screening.

MUTYH Associated Polyposis (MAP): MAP is unusual in that it is inherited in a recessive pattern. This means that someone must inherit a mutation from their mother AND father to be affected. MAP causes multiple bowel polyps, an increased risk of bowel cancer and possibly other cancers. Someone with MAP would be advised to have regular colonoscopies.

NTH1 Associated Polyposis: Variants in NTH1 are also inherited in a recessive pattern. This means that someone must inherit a mutation from their mother AND father to be affected. NTH1 causes multiple colorectal polyps and an increased risk of colorectal cancer. Increased colonoscopic surveillance is advised.

Juvenile Polyposis syndrome (JPS): Juvenile polyposis causes many polyps in the bowel and most people will develop some polyps by the age of 20. As well as an increased risk of bowel cancer JPS also increases the risk of stomach cancer and possibly other cancers. Colonoscopy and endoscopy screening will be recommended. 22% of people with SMAD4 mutations will also have haemorrhagic telangiectasia (malformations of the veins).

Peutz Jeghers Syndrome (PJS): PJS causes polyps in the large and small bowel, as well as ovarian tumours and abnormal colouring around the lips in childhood. PJS causes an increased risk of bowel, breast, pancreatic and other cancers. Mammograms, colonoscopies and other cancer screening will be recommended.

PTEN Hamartoma Tumour Syndrome (PHTS)/ Cowden syndrome: Cowden syndrome can cause bowel polyps, benign skin lesions, benign breast disease, autism and other features. Individuals with Cowden syndrome have an increased risk of bowel, breast, kidney, thyroid, and womb cancers as well as a risk of melanoma. Colonoscopy as well as mammograms, renal MRI, skin examination and thyroid ultrasounds will be recommended. Risk reducing surgery may be considered.

Hereditary Mixed Polyposis Syndrome (HMPS): HMPS is a rare condition which has been identified in families of Ashkenazi Jewish ancestry and which causes multiple bowel polyps of different types as well as bowel cancer. Regular colonoscopies are recommended.

Li Fraumeni Syndrome (LFS): Li Fraumeni syndrome is a relatively rare condition which causes a high risk of cancer in childhood and adulthood: approximately 1 in 5000 to 1 in 20000, people will have LFS. Li Fraumeni syndrome causes an increased risk of sarcomas, brain tumours, breast cancer, adrenal cortical carcinomas and other cancers. Individuals with TP53 pathogenic variants have a 50% risk of developing some type of cancer by age 30 and a lifetime risk of up to 90%. Breast screening with MRI will be recommended. Individuals are also advised to avoid radiation as they have an increased radiation sensitivity.