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Lynch syndrome: Everything you need to know

Lynch Syndrome

What is Lynch syndrome?

Lynch syndrome is an inherited condition that increases a person’s risk of several types of cancer. It used to be known as “hereditary non-polyposis colorectal cancer (HNPCC)” and it is caused by a mutation affecting one of a number of genes. For more information on genetic mutations, click here.

There are four genes that have been linked to Lynch Syndrome, called MLH1, MSH2, MSH6, and PMS2. Mutations in another gene called EPCAM can cause Lynch syndrome by affecting MSH2, the gene next to it, but this is very rare.[1] The MLH1, MSH2, MSH6 and PMS2 genes produce DNA mismatch repair proteins, and these stop cancer from developing by helping to repair any DNA damage that always happens when cells divide. 

All cells have two copies of a gene, one from each parent.  So, a mutation, or spelling error, in one of these genes means that a cell only has one good copy.  As a result, if that cell should suffer a mutation in the one good copy it can no longer repair mismatches and the DNA errors aren’t repaired. The abnormal cells can continue to divide with these mistakes, which can then lead to uncontrolled cell growth. This is why your risk of cancer is increased. This is a bit like a spelling error in an instruction manual - the instructions don’t make sense so whatever you’re building won’t work properly. In this case, the mismatch repair genes don’t work. 

[1] The Royal Marsden, Beginners Guide to Lynch Syndrome, accessed Jan 2020 https://shared-d7-royalmarsden-public.s3-eu-west-1.amazonaws.com/files_trust/s3fs-public/Beginners_guide_to_Lynch_Syndrome.pdf

How is Lynch syndrome inherited?

We have two copies of each LS gene, one from each of our parents, but we only need to inherit one mutated copy to be affected. This means if one of your parents has Lynch syndrome, it is a 50/50 chance whether you inherit it too. You can inherit Lynch syndrome from your mother or your father. In rare cases, you may be the first person in your family to have Lynch syndrome because of a newly arisen mutation (“de novo”). If you have Lynch syndrome, it is a 50/50 chance that each of your children will inherit the mutation, whether they are boys are girls. How common these mutations are in the population differs depending on which gene is mutated, but it is estimated that around 1 out of every 125 people are at risk of Lynch syndrome.[2]

 However, it’s thought 95% of the carriers of these mutations are unaware that they are at risk. 

A genetic mutation like Lynch syndrome is not a guarantee that you will develop cancer, but it does increase the risk that you will be diagnosed with certain cancers in your lifetime. The different gene mutations also impact risk in different ways and for different cancers, so it’s important to speak to your genetic counsellor to fully understand your personal risks.

Risks of cancers in Lynch syndrome vary according to the affected gene.  There is an online resource based upon the study of Lynch syndrome patients called the Prospective Lynch Syndrome Database.  It is open access so anyone, patient, doctor or counsellor can find out their risks, according to which gene, gender, age and if they have already had a cancer. See www.PLSD.eu.

[2] Chapter 14, Lynch syndrome, p.516: WHO Classification of Tumours Editorial Board. Digestive system tumours. Lyon (France): International Agency for Research on Cancer; 2019.

What are my risks if I have Lynch syndrome? 

A genetic mutation like Lynch syndrome is not a guarantee that you will develop cancer, but it gives you an increased risk that you will be diagnosed with certain cancers in your lifetime. 

The table below shows the estimated lifetime risk (up to age 75) for Lynch syndrome. Please email brca@ovarian.org.uk more detailed figures.

Source: (Dominguez-Valentin, Mev, et al. "Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database." Genetics in Medicine 22.1 (2020).

Average risk across all LS mutations- see email brca@ovarian.org.uk for more detailed figures.
Lifetime risk to 75 years Male Female
Any cancer Up to 75% Up to 84%
Colorectal cancer Up to 57% Up to 48%
Ovarian - Up to 17%
Endometrium (womb) - Up to 49%
Stomach, small bowel, bile duct, gallbladder and pancreas up to 22% Up to 13%
Ureter and kidney Up to 18% Up to 19%
Bladder Up to 13% Up to 8%
Prostate Up to 24% -
Brain Up to 8% Up to 3%

Lynch syndrome is also linked to an increased risk of other cancers including:

  • Brain/ central nervous system
  • Small bowel
  • Liver/bile duct
  • Urinary tract
  • Kidney
  • Pancreatic
  • Prostate

It is important to speak to a genetic counsellor to understand your risks in more detail as this will vary depending on your exact mutation.

What is genetic counselling?

Genetic counselling is the process of helping individuals and families understand the medical, psychological, social and reproductive implications of genetic and congenital conditions. Genetic counsellors are healthcare professionals with specialist training in the science of genetic disease, communication skills and counselling. 

Alice Young, Genetic Counsellor at Guy's and St Thomas' Hospital, has written a useful blog on genetic counselling - who it's for, when it's needed, and what happens during a session. Download the blog here.

How do I get tested for Lynch syndrome?

I have colorectal cancer:

If you have a personal diagnosis of colorectal cancer, you are eligible to be tested for Lynch syndrome.

This is because since February 2017, NICE Diagnostics guidance [DG27] has recommended that everyone with colorectal cancer, no matter their age, is offered tested of their tumour initially, followed by a blood testing for Lynch syndrome when necessary.

You can access testing even if you were diagnosed before these guidelines were introduced. Unfortunately, how easy this is to access does vary depending on the area you live in. Please speak to your cancer team to find out more. 

I don’t have colorectal cancer:

If you haven’t had colorectal cancer yourself, you may be eligible if you have had endometrial cancer or a non-serous ovarian cancer under age 65, or one of the rare types of cancer that are more common in Lynch syndrome at any age, such as small bowel, gall bladder, ureter (or bladder before the age of 60).  Anyone with two or more Lynch syndrome-related cancers at any age should be tested.

Otherwise, your eligibility will be based on your family history of cancer.

Speak to your GP if you have:

  • Two or more relatives on the same side of the family with colorectal or Lynch syndrome-related cancers (see the tables above)
  • Any family members diagnosed with colorectal cancer or Lynch syndrome-related cancers (see the tables above) under the age of 50 and/or

  • Three or more relatives with Lynch syndrome-related cancers (see the tables above) on the same side of the family

If these apply to you, you can speak to your GP about being referred for genetic counselling where you can talk about your risks, screening and prevention options. If you did go ahead with genetic testing, this takes place through a simple blood test.

Please see here for more information about cancer risk reduction and screening.

Be symptom aware

For details on the signs and symptoms of these cancers, see here:

If you need support, please contact brca@ovarian.org.uk or the support group Lynch Syndrome UK.

With thanks to Dr Ian M Frayling MA MB BChir PhD FRCPath Hon.FFPath(RCPI) FEBLM Consulting Genetic Pathologist to St Mark's Hospital, London & St Vincent's Hospital, Dublin. Honorary Senior Clinical Research Fellow, Inherited Tumour Syndromes Research Group. Member of Council & Honorary Treasurer, InSiGHT and UK Cancer Genetics Group Honorary Adviser to Lynch Syndrome UK and Lynch Syndrome Ireland.