What Is Lynch Syndrome?

Some diseases have a tendency to run in families and cancers are no exception. Cancer syndromes that are genetic diseases can give you a much higher chance than normal of developing certain types of cancers. Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is an example of this and is the most common cause of familial colorectal cancer.¹ 

Overview

Lynch syndrome is the most common cause of familial colorectal (bowel) cancer, however, only 2-4% of patients with this type of cancer have Lynch syndrome.¹

Lynch syndrome is also associated with increasing the risk of developing other cancers such as endometrial, ovarian, kidney, small bowel, brain and stomach cancer.² People with Lynch syndrome typically develop these cancers at a younger age than those who do not have it, for example, the average age of diagnosis of colorectal cancer in someone with Lynch syndrome is 44 years old.³

Causes of lynch syndrome

Cancers occur for a multitude of reasons but typically the result is that there is a mutation in the DNA in certain cells. Mutations cause cells to multiply and grow out of control, interfering in negative ways with how your body should work. However, your body has a multitude of ways of preventing this from happening (mutations in your DNA do occur naturally every day and your body actively destroys many cells that could potentially develop into cancer cells)¹

One way your body achieves this is by heavily regulating the process of DNA replication. This is where your body makes copies of your DNA and it is an important step in creating new cells. Your DNA codes for different types of proteins and some of these proteins are responsible for a process called mismatch repair.¹

In Lynch syndrome, there is a mutation in the DNA mismatch repair genes (mmr genes). Under normal circumstances, mmr genes produce proteins that rigorously check and correct the copied DNA during the process of DNA replication. In Lynch syndrome, this does not occur and with each replication, damaged DNA will accumulate, therefore creating cells with more mutations. This accumulation inevitably leads to people with Lynch syndrome being more susceptible to cancer.¹

Lynch syndrome is inherited during the conception of the foetus via an egg/sperm carrying the corresponding DNA and is an example of a germline mutation. This means that if you inherit the Lynch syndrome mutation, it will be present in every cell of your body and can be passed on to future children. Lynch syndrome is also inherited in a dominant fashion (only need one copy of the mutated gene to have this disorder) and a parent with Lynch syndrome has a 50% chance of passing the syndrome onto their children.¹

Signs and symptoms of Lynch syndrome

The symptoms of Lynch syndrome will effectively be the same symptoms of the cancers it typically causes namely colorectal (bowel) cancer. Other cancers that may develop include endometrial, ovarian, and gastric cancer. 

Symptoms to look out for generally include:

• Unexplained weight loss
• Blood in the stool
• Sudden loss of appetite
• Excessive, unexplained fatigue
• Unexplained abdominal pain
• Change in bowel habit
• Postmenopausal vaginal bleeding
• Bloating^2,3,4

However, Lynch syndrome only makes up a small proportion of those who get cancer so other, more specific signs that could indicate you may have it or are at risk of it include:

• Developing colorectal cancer or endometrial cancer before the age of 50
• Having an immediate family member (parents, brothers, children) who develops Lynch syndrome-associated cancers before the age of 50
• Multiple relatives developing lynch syndrome associated cancers¹

Management and treatment for Lynch syndrome

Lynch syndrome is typically treated after diagnosis in one of two ways: 

• Asymptomatic Lynch syndrome - no symptoms are present but there is a known family history of Lynch syndrome/lynch syndrome-associated cancers 
• Symptomatic Lynch syndrome - symptoms will develop as a result of acquiring a case of Lynch syndrome associated-cancer (every patient with colorectal/bowel cancer receives testing for Lynch syndrome) 

If you have suspected asymptomatic Lynch syndrome, you may be referred for genetic counselling/testing. If Lynch syndrome is suspected due to family history, it is likely that previous genetic tests on your affected relative’s tumours will be checked. If genetic tests return positive for Lynch syndrome for your family member, you should be offered genetic testing for yourself. This may include germline cell (egg/sperm cell) testing for the presence of the mutations.⁵

As Lynch syndrome typically causes colorectal cancer, patients with confirmed Lynch syndrome will undergo colonoscopic surveillance. This is where they have regular colonoscopies to check for the presence of any tumours in the bowel (usually once every 2 years).⁵

Younger patients with confirmed Lynch syndrome may also be offered surgery to remove most of the colon because the risk of developing colorectal cancer is so high over their lifetime. Women over the age of 40 may also be offered a hysterectomy which is an operation to remove their uterus to prevent endometrial cancer. Aspirin may also be offered as it has been shown that daily aspirin can prevent colorectal cancer in Lynch syndrome patients.^5,6

If you have symptomatic Lynch syndrome, and therefore, a diagnosis of the type of associated cancer, your doctor should offer you treatments/a combination of treatments such as:

• Surgery 
• Chemotherapy 
• Radiotherapy

FAQs

How is Lynch syndrome diagnosed?

Lynch syndrome is diagnosed with a test called immunohistochemistry testing. This is a test that detects how much MMR proteins are present in the colorectal cancer tumours with low or absent levels indicating Lynch syndrome. Lynch syndrome can also be diagnosed by testing your blood or saliva, using these samples to identify mutations in your genes that are characteristic of Lynch syndrome.⁷

How can I prevent Lynch syndrome?

Lynch syndrome is inherited so it cannot be prevented. However, the process of cancer surveillance by getting a colonoscopy every 2 years can increase the likelihood that if you are to develop bowel cancer, it is caught early. This will give the best outcomes. Also taking daily aspirin can also help prevent the development of bowel cancer. Surgery to remove most of the colon or the uterus can also prevent future colorectal or endometrial cancer.⁶

Who is at risk of Lynch syndrome?

You are most at risk of Lynch syndrome if you are someone who has relatives who have developed bowel cancer or other Lynch syndrome-associated cancer at a relatively young age (prior to 50). More so if there are multiple members of your family who have developed the associated cancers.

How common is Lynch syndrome?

It is estimated that in the UK 175,000 (or 1 in every 400 people) have lynch syndrome.⁵

When should I see a doctor?

If you show the symptoms of bowel cancer such as blood in your stool, a change in bowel habits, abdominal pain, unexplained weight loss or any of the symptoms mentioned previously in this article you should see a doctor as soon as possible to rule out any potential cancer. However, you should also see a doctor if you have a few relatives who developed cancers associated with Lynch syndrome at a young age especially if they are 1st-degree relatives. 

Summary

Lynch syndrome causes a person to be highly susceptible to cancer at much a younger age than most other people. It mainly increases the risk of developing colorectal and endometrial cancer and typically runs in families and affects multiple generations. Therefore, it is important to see a doctor as soon as possible if you have a family history who has developed cancers that are associated with Lynch syndrome. This is so that you can get genetic testing and if it comes back positive, begin surveillance to reduce the chances of developing bowel cancer.