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What is Lynch syndrome?

Lynch syndrome is a hereditary condition that follows an autosomal dominant inheritance pattern. If one parent carries a Lynch syndrome-related genetic mutation, each child has a 50% chance of inheriting it.

Lynch syndrome in brief

Lynch syndrome is a hereditary genetic mutation that is passed from a parent to their child with a 50% probability.
It is associated with alterations in the MMR (mismatch repair) genes—MLH1, MSH2, MSH6, and PMS2—which are involved in repairing DNA errors and can increase the risk of developing cancer.
Mutation carriers are often diagnosed with cancer at a younger age than average, particularly colorectal and uterine cancers.
However, not all carriers of the genetic mutation develop cancer, and regular surveillance and screening help identify and manage the risk.

Lynchin syndrooma -opas

What causes Lynch syndrome?

Lynch syndrome is inherited in an autosomal dominant manner. If a parent (either mother or father) carries the Lynch syndrome genetic mutation, each of their children has a 50% risk of inheriting it. Mutations predisposing to Lynch syndrome are known to occur in four genes belonging to the mismatch repair (MMR) group, which repairs DNA replication errors. These four MMR genes are MLH1, MSH2, MSH6, and PMS2.

A properly functioning MMR system recognizes and repairs mismatched base pairs that occur during DNA replication (duplication). However, if one allele of an MMR gene is already mutated in all cells of the body, and the second allele becomes inactivated in an individual cell due to biochemical modification or a new mutation during cell division, the repair system will no longer function in that cell. This can lead to consequences that promote the development of cancer.

Mutation carriers have a higher risk of developing cancer at a young age

Because this is an autosomal dominant germline mutation, first- and second-degree relatives may experience a higher-than-normal incidence of cancers occurring at a young age—most commonly colorectal and uterine cancers. It is characteristic of Lynch syndrome that mutation carriers are diagnosed with multiple distinct primary tumors during their lifetime.

Colorectal cancer is diagnosed in mutation carriers at an average age of 41–61, which is significantly younger than sporadic colorectal cancers (cancers with no identifiable hereditary predisposing genetic mutation), where the average age of diagnosis is 69.

The level of cancer risk depends on the specific gene involved

The level of cancer risk depends on the gene in which the mutation is located. Mutations in the MLH1 and MSH2 genes are the most common, and the lifelong risk associated with them is the highest. The lowest cancer risk is associated with the PMS2 gene.

Childhood cancers associated with the syndrome can occur if both parents are carriers and the child happens to inherit an MMR mutation from both parents (constitutional mismatch repair deficiency, CMMRD). To date, no such cases have been identified in Finland.

Not all mutation carriers will necessarily develop cancer

Not everyone who inherits Lynch syndrome will necessarily develop cancer. The Finnish Lynch Syndrome Research Group is currently investigating how external factors (such as diet, exercise, etc.) influence the risk of developing cancer. Information about this and other studies by the LS group can be found on the research group’s website.

PLSD Calculates the risk of different cancers for different Lynch syndrome genetic mutations. The estimator also takes age and sex into account.

PREMM-laskuri Estimates the probability of Lynch syndrome based on an individual’s background information.

Lynchin syndrooma -opas

Genetic testing

If you are currently healthy but suspect you may carry a Lynch syndrome genetic mutation and wish to be tested, you can contact the Finnish Lynch Syndrome Registry.

Testing is available for adults

Testing is available only after reaching the age of 18, even if it is known that one of your parents is a mutation carrier. To seek testing, you can contact either the clinical genetics department of your local university hospital or the Lynch Syndrome Research Group (noora.hakkinen@hus.fi or kirsi.pylvanainen@ksshp.fi).

Everyone has the right to choose whether to be tested

Everyone has the right to choose the timing of their testing and whether they want to be tested at all. However, it is important to keep in mind that it is the responsibility of a mutation carrier to ensure that their children and other relatives receive sufficient information about the hereditary cancer predisposition. This allows them to seek genetic counseling if they wish. Testing is the only way to know for certain whether you are a mutation carrier.