Lynch syndrome

What is Lynch syndrome?

Lynch syndrome is an inherited condition due to a gene fault that increases a person’s risk of developing certain types of cancer.

When a person has Lynch syndrome, it means that a gene involved in repairing specific DNA errors does not work properly. As a result, DNA damage can build up in certain cells of the body. If the DNA damage is not repaired, the cells can start to grow and divide in an uncontrolled way. This can lead to cancer.

Having a gene fault associated with Lynch syndrome does not necessarily result in developing cancer.

Which genes are involved?

The genes known to be involved in Lynch syndrome are called ‘mismatch repair genes’. There are four of these genes currently known to be involved: MLH1, MSH2, MSH6, and PMS2. Lynch syndrome can occur when any one of these genes does not work properly. So far, faults in any of these four genes are known to be associated with an increased risk of Lynch syndrome-related cancers. There may be other genes involved in Lynch syndrome that are yet to be identified.

How common is Lynch syndrome?

It has been estimated that over 80,000 people in Australia (or 1 in 280 people) carry a mismatch repair gene fault associated with Lynch syndrome. However, as the condition is usually only found when people undergo genetic testing, there may be people with Lynch syndrome who have not yet been diagnosed.

Which cancers are seen in people with Lynch syndrome?

The two cancers that are most common in people with Lynch syndrome are:

colorectal cancer (large bowel cancer)
endometrial cancer (cancer of the uterus lining).

Lynch syndrome also increases a person’s risk of other types of cancer, including: ovarian cancer, cancers of the urinary tract including bladder cancer, gastric (stomach) cancer, small bowel (small intestine) cancer, hepatobiliary cancer (cancers of the liver, gall bladder and bile duct), kidney cancer, brain cancer and skin cancer.

Lynch syndrome may also be associated with an increased risk of pancreatic cancer and prostate cancer.

What is the risk of cancer in people with Lynch syndrome?

Having Lynch syndrome does not mean that a person will definitely develop cancer. However, the risk of developing cancer is higher than for people who do not have Lynch syndrome.

Cancer may also develop at a younger age than in the general population.

The level of risk of developing cancer depends on which mismatch repair genes are faulty. The risk of developing cancer is much lower for people who have a fault in the PMS2 gene compared with those who have faults in other mismatch repair genes.

The level of risk is also different for different types of cancer.

For example:

about 1 in 3 men and women with Lynch syndrome will develop colorectal cancer before the age of 70 years (compared to about 1 in 30 men and 1 in 40 women in the general population)
about 1 in 3 women with Lynch syndrome will develop endometrial cancer before the age of 70 years (compared to about 1 in 100 women in the general population).

Family history and Lynch syndrome

Lynch syndrome is an inherited condition. There is a 1 in 2 chance that a faulty gene will be passed on from a parent to their child. The faulty gene can be inherited from either the mother or the father.

Conversely, there is a 1 in 2 chance that a faulty gene will not be passed on from a parent to their child, so not all children from the same parents will necessarily be affected.

When reviewing someone’s family history of Lynch syndrome-associated cancers, a doctor will look at how many members of the family have one or more of the cancers listed above, at what age they were diagnosed with the cancer, and how the affected family members are related. A family history of these cancers is more likely to be due to Lynch syndrome if:

at least three relatives* are affected (two of whom must be directly related to each other^#), and
at least two successive generations are affected, and
at least one relative was diagnosed before the age of 50 years.

These family characteristics do not necessarily mean there is a mismatch repair gene fault in the family, but they do make it more likely that this is the case.

* This includes extended relatives such as brothers and sisters, cousins, aunts and uncles, second cousins, great-aunts and uncles, and great grandparents.

^# This could be a parent and child or two siblings (i.e brothers or sisters).

Testing for Lynch syndrome

Deciding whether to be tested for Lynch syndrome

If a family history of cancer suggests that a person may have Lynch syndrome, genetic assessment (also called genetic counselling) should be recommended. This involves more comprehensive assessment of family history to find out more about any cancers in relatives and the age at which they were diagnosed. If Lynch syndrome is likely, then testing for a fault in one of the mismatch repair genes can be done.

Testing for a fault in one of the mismatch repair genes should be considered if he or she develops colorectal cancer or endometrial cancer at an early age, before age 50 years.

Tumour tissue testing

If a person has a Lynch syndrome-associated cancer, the cancer cells may be tested with special stains to see if there are signs of Lynch syndrome. If so, then genetic testing is offered to test for a mismatch repair gene fault.

Genetic testing

Genetic testing for a mismatch repair gene fault involves testing the blood of a person with one of the cancers associated with Lynch syndrome or of a person with a family history of Lynch syndrome-associated cancers. This blood test will look for any faulty copies of the mismatch repair genes in the DNA of the sample.

The results of the test will be used to discuss with the patient the significance of sharing this information with other members of the family.

If no gene fault is found, no further testing will be recommended for family members.
If a faulty gene is found, genetic testing is generally recommended for other direct relatives (parents, sisters, brothers and/or children) as they may also carry the faulty gene. It is important to remember that a positive test in one family member does not mean that every other member of the family will be affected.

Genetic testing in family members is recommended even if they do not have cancer themselves as there are implications for cancer screening and early diagnosis.

What you can do if you have Lynch syndrome?

If genetic testing shows that a person has a faulty mismatch repair gene, this means that he or she is at increased risk of developing Lynch syndrome-associated cancers. Regular check-ups will be recommended to look for early signs of cancer. This means that if cancer does develop, treatment can start as soon as possible.

The most common check-up is a colonoscopy to look for changes in the bowel.

Other check-ups may be recommended depending on the person’s individual or family history of cancer and other diseases. Tests are not available to look for all of the cancers associated with Lynch syndrome such as endometrial cancer, hence it is important that women are aware of early signs and symptoms of endometrial cancer. For some people with Lynch syndrome, surgery or other treatment may be recommended to reduce the risk of cancer.

People who are at high risk of colorectal cancer associated with Lynch syndrome may be advised to take aspirin to reduce their risk. Hysterectomy, an operation to remove the uterus, may be advised for some women to reduce their risk of endometrial cancer. Maintaining a healthy weight, eating a healthy diet, physical activity and other lifestyle behaviours are important in reducing the risk of many cancers including those associated with Lynch syndrome.

More information

Lynch Syndrome Australia provides information about Lynch syndrome as well as links to useful resources
Family Cancer History mapping tool helps people review their family history; it is recommended that when completed, this tool is discussed with a GP or other health professional
eviQ guidelines provide up to date information about the management of Lynch syndrome
The NSW Centre for Genetics Education has a list of Familial Cancer Clinics across Australia
Cancer Council clinical practice guidelines. Prevention, early detection and management of colorectal cancer: Lynch syndrome.

Relevant Cancer Australia Position Statements: