Lynch syndrome

Lynch syndrome is a genetic disorder, also called HNPCC syndrome (Hereditary Non-Polyposis Colorectal Cancer).

It is due to the mutation of one of the four genes hMLH1, hMSH2, hMSH6 or PMS2, which normally ensure the diagnosis and repair of DNA mismatches during its replication.

This mutation is transmitted in the family according to an autosomal dominant mode.
- Autosomal: transmission is not sex-linked. Both women and men can be carriers and transmitters.
- The risk of transmission is 50%
- Dominant: inheriting the mutation makes you exposed.

This predisposition leads to an increased risk of developing cancers, first and foremost nonpolyposis colorectal cancer (Human nonpolyposis colorectal cancer [HNPCC]), endometrial cancer in women, and to a lesser extent, cancer ovary, small intestine, stomach, urinary and hepatobiliary excretory tract. Thus, the cumulative risk of developing colorectal or endometrial cancer at age 80 is 20 and 40%, respectively.

Lynch syndrome should be suspected clinically when there is:
- At least three relatives with narrow spectrum cancer
- One is first degree related to one of the other two
- At least two generations affected
- At least one cancer diagnosed before the age of 50
- A familial adenomatous polyposis is excluded
- Tumors need to be checked
These criteria are defined as the Amsterdam Criteria 2.

This syndrome must also be systematically sought in the event of endometrial cancer occurring before the age of 50 or whatever the age if a first-degree relative has suffered from colorectal cancer or cancer of the LYNCH spectrum.
Anatomopathology laboratories routinely search for this syndrome using an immunohistochemical test that evaluates the expression of the proteins coded by these genes.
In the event of a positive test, in the event of an evocative family tree, an onco-genetic consultation is necessary as well as confirmation of the anomaly by a search for mutations in molecular biology.

Early identification of carriers of the mutation is important because:
- It allows screening or prevention of other cancers
- It makes it possible to diagnose affected relatives and offer them screening or prevention of the main cancers.

People affected by this syndrome must therefore benefit from specific and regular monitoring and follow-up.

Current recommendations call for the following monitoring:
- Performing a colonoscopy every two years from the age of 20.
- Realization of an esophagogastro-duodenal fibroscopy during the realization of the first colonoscopy
- Annual gynecological screening, including clinical examination, ultrasound and endometrial sampling

It is also possible to perform a non-conservative total hysterectomy from the age of 40 (INCa recommendations 2009). In practice, these interventions are mainly performed after 45 years, because the risk of endometrial cancer before this age is low; and because the consequences of hysterectomy are less at this age. Different proposals can nevertheless be made, depending on the age of onset of cancer in the family or the woman's personal history. The dialogue with the onco-genetics team is important.