Lynch syndrome

Lynch syndrome

What is Lynch syndrome?

Lynch syndrome is an inherited disorder that increases the risk of cancer, most importantly the risk of large bowel cancer (colorectal cancer) and of the lining of the uterus (endometrial cancer). To a lesser extent, persons  with Lynch syndrome are at increased risk of other types of cancer, such as cancer of the ovaries or cancer of the stomach. Characteristics of Lynch syndrome include a relatively young age at diagnosis of the cancer (e.g. mean age at diagnosis is before fifty years), multiple tumours in one person and familial occurrence of colorectal and/or endometrial cancer, most typically in multiple generations. Although people that carry the genetic predisposition for Lynch syndrome are at increased risk of cancer, not all of them will actually develop cancer.

Lynch syndrome is the most common form of inherited colorectal cancer. Out of every 100 persons  with colorectal cancer, 3 to 5 have Lynch syndrome. Developing large numbers of colonic polyps is not a feature of Lynch syndrome, however, some polyps (adenomas) may occur. In the past, Lynch syndrome was therefore called Hereditary Non-Polyposis Colorectal Cancer (HNPCC) to discriminate it from the inherited forms of colorectal cancer with multiple colonic polyps (i.e. polyposis).

What causes Lynch syndrome?

Lynch syndrome is an inherited disorder, caused by a mutation in one of the following four so called DNA mismatch repair genes: the MLH1, MSH2, MSH6 or  PMS2 gene. In addition to this, specific aberrations in the EPCAM gene lead to Lynch syndrome due to inactivation of the MSH2 gene. DNA mismatch repair plays an important role in the repair of errors in the building blocks of DNA that can occur when new cells are being formed in the body. Mutations in any of these genes increase the risk of DNA errors in the new cells, which may eventually lead to uncontrolled cell growth and cancer.

How is Lynch syndrome inherited?

Lynch syndrome is inherited in an autosomal dominant way, which means that each child of a person with Lynch syndrome has a 50% risk of inheriting the mutation. Both men and women can pass the mutation on and inherit it. Please note that by inheriting the mutation, an increased risk of cancer is inherited, not the disease itself. Not all persons who inherit a mutation causing Lynch syndrome will eventually develop cancer.

What are the surveillance / preventive options?

Persons with Lynch syndrome are advised to have their colon (large bowel) checked regularly by coloscopy. In addition, women with Lynch syndrome may benefit from regular gynaecological check-ups. For some patients, preventive surgery of the uterus and ovaries may be an option. When colorectal cancer is diagnosed in a person with Lynch syndrome, the optimal  treatment may differ from persons  without Lynch syndrome. This may concern the choice of surgery or chemotherapy or the use of specific drugs. Therefore, persons with Lynch syndrome are recommended to seek expert advice for their screening and, if necessary, treatment.

 

Clinical practice guidelines

Endorsed by ERN GENTURIS*

* ERN GENTURIS uses AGREE II as a tool for the endorsement of guidelines. The quality of the guideline is evaluated through assessing the rigor and transparency of the guideline development process. The content of the guideline is not evaluated, although selection of the guideline for endorsement includes expert opinion on the usefulness of the content of the guideline.

Lynch syndrome:

Hereditary colorectal cancer:

 

Care pathway

Currently unavailable

 

Patient journey

Patient journey - Lynch syndrome