Date issued: April 2020
For review: April 2022
Ref: A-437/MB/Medical Specialities/Lynch Syndrome
What is Lynch syndrome (also known as Hereditary Non-Polyposis Colon Cancer, HNPCC)?
Lynch syndrome is caused by a misprint (a spelling mistake) in one of four genes. Normally, these genes help to protect us from cancer. If one of them contains a misprint, it cannot function properly. This means that the person has a higher cancer risk than other people. The most common cancers in Lynch syndrome are in the bowel (colon) and the womb (endometrium). The cancer risk is high, but some people with Lynch syndrome never develop cancer.
Some other cancers also occur more frequently in Lynch syndrome. For example: stomach, small bowel, bladder, prostate and pancreas. The risk of these other cancers is far lower than the risk of bowel or womb cancer, usually, no more than 5% (1 in 20 people). The risk of prostate cancer may be a little more than this. The precise risk will depend on which gene is involved in your family.
What causes Lynch syndrome?
Lynch syndrome occurs when a person is born with a misprint in one of the mismatch repair genes, (called MLH1, MSH2, MSH6 or PMS2). Most of these misprints occurred many generations ago, so Lynch syndrome is usually inherited from a parent. If there is a damaging (‘pathogenic’) misprint in one of the mismatch repair genes this causes Lynch syndrome. (Please note that we all have many misprints in our genetic codes, but most are harmless.)
How is Lynch syndrome inherited?
We each have many thousands of genes, which are in pairs. We inherit one copy of a gene from our mother and the other from our father, so we end up with two copies of every gene. In turn, just one copy is passed to a child (who receives a second copy from the other parent). A parent with Lynch syndrome will have one normal copy of the gene in question and one misprint. Only one of these will pass to a child. Therefore, there is a 50% (1 in 2) chance that a child will inherit a misprint from an affected parent.
The misprinted gene “dominates” (has a stronger effect) over the normal copy, so this pattern of inheritance is called “autosomal dominant”. The diagram on the next page shows how this works.
Can my relatives have a test for Lynch syndrome?
Yes, providing we have found a gene misprint in the family. Relatives can be referred to their local Clinical Genetics Service to discuss this. We usually offer testing from age 18 and we advise people to take their time in deciding when to have a test. The test itself requires a blood sample.
What does a genetic test tell us?
It tells us whether the genetic misprint is present or absent in that person.
If a person does not have the misprint, they do not have Lynch syndrome, and their children cannot have the misprint either. Their cancer risk will be the same as the background population.
If a person does have the misprint, they are at high risk of cancer, especially bowel and womb.
People who test positive for Lynch syndrome
Lynch syndrome means that a person has a high risk of developing one or more cancers. It is important to have regular bowel screening, usually by colonoscopy. We recommend a colonoscopy every 18 months – 2 years. Many bowel cancers develop from harmless growths called polyps (adenomas). If any polyps are detected, they can usually be removed very easily during the colonoscopy. In the general population, it takes many years for a polyp to develop into a cancer. However, in Lynch syndrome, this can happen more quickly and that is why we recommend a colonoscopy every 18 months – 2 years.
Womb (endometrial cancer)
There is no proven method of screening for womb cancer. Many women who are at high risk consider having a hysterectomy once their families are complete, or around the age of 40. There is also an increased risk of cancer of the ovary, so it may be appropriate to consider having the ovaries removed as well, particularly if a woman is close to the age of menopause.
Is any other screening necessary?
One in 5 people have a bacterial infection in their stomach called Helicobacter pylori (Pylori). This may slightly increase the risk of stomach cancer (and ulcers) so we recommend that you ask your GP for a test. If the infection is present, it can be treated easily by a course of antibiotics.
There is an increased risk of prostate cancer, so men who have Lynch syndrome may wish to have annual screening by taking part in a research study called IMPACT. This is a simple blood test.
Is there anything else I can do to lower my risk?
Several studies, mainly in the general population, have shown that aspirin lowers bowel cancer risk. We do not yet know what dose or duration gives the best risk reduction. A research study (called CAPP3) is in progress, which we hope will answer these questions. The study has now closed to new patients, and it will be several years before we know the outcome.
In the meanwhile, you may wish to consider taking daily aspirin; this will have been discussed with you at your clinic appointment. Please talk to your GP before starting in case there are any personal medical reasons why this would not be advised (see further info and links below)
There is good evidence that diet may lower cancer risk. It is sensible to eat plenty of fresh vegetables, fruit and nuts, and to avoid high amounts of animal fat, especially red and processed meat, a ‘junk food’ diet is definitely associated with a higher risk of bowel cancer. Being overweight increases the risk of cancer, as does smoking. It is advisable to avoid excessive alcohol intake. Regular exercise lowers bowel cancer risk, and helps in keeping weight under control. All these things are important to maintain good general health.
Are there any symptoms I should look out for?
Bleeding from the back passage, change of bowel habit, diarrhoea or constipation (persisting for more than a couple of weeks) should be reported to your doctor. Although these symptoms often have an innocent cause, they sometimes indicate an early bowel cancer. Leaflets about this are available; please ask us or your doctor if you need more information.
Women should report any unusual vaginal bleeding. This is usually obvious after the menopause, but any unusually heavy or persistent bleeding before the menopause should also be reported.
Otherwise, we simply recommend a common sense approach to symptoms; any unexplained loss of weight or appetite, or any persistent pain or discomfort in the tummy, or blood in the urine should be mentioned to your doctor, who will be able to decide whether any investigations are necessary.
The most important thing is to continue with regular bowel screening, which our colleagues in gastroenterology or surgery will arrange. If you do not receive an appointment for a repeat colonoscopy every 18 months – 2 years, please contact the gastroenterology department first, but if you are concerned do please let us know.
Follow up in the genetics clinic will depend on your own particular circumstances. Even if no routine follow up is planned, please contact us if you have questions or would like another appointment.
- Dr Paul Chrisp, director of the Centre for Guidelines at NICE, in new draft guidance said: “The independent committee looked at evidence from a multi-country randomised controlled trial, which showed taking daily aspirin for more than two years reduces the risk of colorectal cancer in people with Lynch syndrome. “While there are risks associated with long-term aspirin use, the committee agreed that the benefits are likely to outweigh any potential harms.” “It is important that clinicians and patients discuss the potential harms and benefits of long term aspirin use so that an informed decision can be made.”