What it is
Lynch syndrome is caused by an inherited alteration in one of the genes that correct DNA errors: MLH1, MSH2, MSH6, PMS2 or EPCAM (which switches off MSH2). It accounts for around 3 % of all colorectal cancers and is the most common hereditary cause. It is passed on in an autosomal dominant way: each son or daughter of a carrier has a 50 % chance of inheriting it, whether male or female.
People with Lynch syndrome have a higher risk of colon cancer (over a lifetime, between 10 % and 50 % depending on the gene; much lower with PMS2 and MSH6 than with MLH1 and MSH2), of endometrial cancer in women, and to a lesser extent of ovarian, stomach, small bowel, urinary tract, pancreatic, biliary, brain and skin cancers. Tumours tend to appear at younger ages.
How it is suspected
- The tumour is dMMR / MSI-H (guidelines recommend testing this in all colorectal cancers). If there is also MLH1 methylation or a BRAF V600E mutation, the origin is usually sporadic rather than hereditary.
- Colon or endometrial cancer before the age of 50.
- Several relatives with colon, endometrial or other Lynch-spectrum cancers, or one person with two different tumours.
How it is confirmed
In the genetic counselling clinic (familial cancer unit or oncology) your family history is reviewed and a blood test looks for the alteration in the syndrome's genes. The result takes weeks. Beforehand you are told what each possible result means, including "variants of uncertain significance", which are neither positive nor negative. The test is free in the Spanish public health system and the results are protected.
What changes if it is confirmed
For you
- Colonoscopy every 1-2 years for life (starting at age 20-25 in healthy carriers). Lynch polyps grow quickly; frequent colonoscopy clearly reduces the risk of cancer and of dying from it.
- Women: yearly gynaecological assessment and, once childbearing is complete, preventive removal of the uterus and ovaries can be considered (from around age 40, depending on the gene).
- Depending on the gene and the family: periodic gastroscopy, urine tests, skin checks.
- Aspirin: the CAPP2 study showed that taking daily aspirin for at least 2 years reduces the risk of colon cancer in Lynch syndrome. Guidelines include it; the dose and whether it suits you (bleeding risk) are for your doctor to decide.
- If you have already had colon cancer, the surgeon may propose a more extensive colectomy to reduce the risk of a second tumour; it is an individual decision.
- If the tumour is dMMR, immunotherapy works particularly well (see the guide MSI-H / dMMR).
For your family
This is the most valuable part of the diagnosis: your parents, siblings and children (first-degree relatives) can have a test targeted at your family's specific alteration ("cascade testing"). Those who have not inherited it have the general population risk and need no special surveillance; those who have start colonoscopies in time and prevent cancer. The genetic counselling unit helps you communicate it, sometimes with a letter you can give to your relatives.
The emotional side
Receiving this diagnosis brings guilt ("I may have passed it to my children"), fear and sometimes family conflict about who wants to know and who does not. None of that is unusual. Remember that the alteration is neither chosen nor caused, that knowing is what makes prevention possible, and that each adult relative decides for themselves whether and when to be tested. Patient associations and hospital psycho-oncologists know this situation well.
What to ask at your appointment
- Is my tumour dMMR/MSI-H? Has a sporadic cause been ruled out (MLH1 methylation, BRAF)?
- Can you refer me to genetic counselling? How long does it take?
- If confirmed, which gene do I carry and which surveillance schedule applies to me?
- How is testing done for my relatives, and from what age?
- Would aspirin suit me? And more extensive or preventive surgery?
