Lynch syndrome is a synonym for hereditary non-polyposis colorectal cancer (or HNPCC for hereditary non-polyposis colorectal cancer). (1)

It is the most common form of inherited colorectal cancer.

Its inheritance is autosomal dominant. This form of transmission of the disease reflects the fact that the gene in question is carried by an autosome (non-sexual chromosome). In addition, the presence of a single mutated allele is sufficient for the development of the disease. The genetic transmission of Lynch syndrome therefore requires that one of the two parents of the subject has the disease. Indeed, an affected person has a risk of transmitting the pathology up to 50%.

This syndrome increases the risk of developing certain types of cancer, particularly cancers of the colon (large intestine) and rectum, hence its name colorectal cancer.

In addition, patients with this syndrome also have an increased risk of developing cancers affecting the stomach, small intestine, liver, billary bladder, urinary tract, brain or even the skin.

Women with this syndrome also have an additional risk of developing cancer of the ovaries or endometrium (inner lining of the uterus). (2)

Some people can also have this syndrome without the onset of the disease: it is the mild form. In this case, we will talk about colon polyps. These are generally benign tumors that develop within a mucous membrane. Here, these polyps therefore develop in the intestinal mucosa of the colon. These “mild” patients see bowel disorders appear earlier but with lesser consequences compared to people with hereditary colorectal cancer without polyposis in its general form. (2)

People with Lynch syndrome are more concerned with the potential development of colorectal cancer, especially if it starts before the age of 50. (3)

The tumor located in the colon or rectum is usually treated with surgery. A sample of the tumor tissue is then analyzed to determine if it is caused by Lynch syndrome. (3)

The diagnosis of the disease is based on a set of criteria.

In the event that colorectal cancer is diagnosed in a person, tests are performed to determine the origin and possibly the underlying presence of Lynch syndrome. (1)

There is an additional risk that the tumor is from Lynch syndrome if:

– at least 3 people from the same family have been diagnosed positive for the development of cancer linked to Lynch syndrome;

– the patient presents family ties over two generations and in the first degree with people who have developed the disease;

– the cancer developed before the age of 50.

The symptoms associated with the pathology mainly affect the intestines. (4)

The clinical manifestations are reflected by:

– intense and unexplained fatigue;

– an unusual bowel disorder and pain: bleeding in the stool, the presence of mucus in the stool, etc.

– unexplained weight loss.

In addition to these disorders, women can also experience bleeding from the uterus.

The diagnosis of uterine cancer in women may be the underlying cause for the development of Lynch syndrome. (4)

A visit to a general practitioner is strongly recommended if the presence of these symptoms is marked. In this sense, he can direct the diagnosis to the detection of Lynch syndrome or refer the person to a geneticist in order to confirm or not the development of HNPCC. (4)

Lynch syndrome is an inherited disease.

The origin of this disease is therefore an autosomal dominant genetic transmission.

The mutated genes involved in the development of the disease are part of the family of DNA repair genes. Indeed, during DNA replication, nucleotide base mismatches (basic elements of the double double-stranded DNA chain) can occur. In this sense, repairs of these mismatches (pairwise association faults) are possible. These corrections of anomalies are effective by proteins derived from the genes: MSH2, MLH1, MSH6 and PMS2.

Mutations within these genes increase the risk of developing Lynch syndrome.

Indeed, these mutations therefore prevent the correction of errors made during DNA replication. This results in the accumulation of genome errors and the continued development of abnormal cells. This phenomenon therefore leads to the development of a tumor. (1-2)

Mutations within the EPCAM gene can also lead to the development of the disease. Indeed, this gene is closely linked to the MSH2 gene and can thus deactivate it. This leads to disruptions in DNA repair and therefore an accumulation of genetic errors.

Although these genetic mutations predispose people to developing Lynch syndrome, not all cause it. (2)

Lynch syndrome is inherited in an autosomal dominant fashion. Either, the presence of at least one mutated allele for these genes can lead to the development of the diseased phenotype. (2)

Or, if a person has the mutated allele for one of these genes linked to the disease, that person has a 50% risk of transmitting it to his descendants. (4)

The risk factors for hereditary nonpolyposis colorectal cancer (or Lynch syndrome) are genetic.

Lynch syndrome being an inherited genetic disease with autosomal dominant transmission.

Either, the presence of a single copy of the mutated allele for the genes relating to the disease in a person is sufficient to develop the diseased phenotype.

In this sense, the presence of the mutated allele in one of the two parents entails a 50% risk that the child will develop the pathology.

A differential diagnosis can be established from the different symptoms associated with the disease (intestinal symptoms, intense and unexplained fatigue, etc.)

A diagnosis follows based on the genetic heritage of the family. Indeed, the presence of at least one mutated gene in an individual can lead to an increased risk of transmitting the disease to the offspring by up to 50%.

In the event of a positive diagnosis for the presence of mutations in the MSH2, MLH1, MSH6, PMS2 or EPCAM genes, colonoscopic monitoring is strongly recommended from the age of 20.

A gynecological follow-up is also prescribed for women after 30 years.

As this disease is genetically inherited, there is no preventive treatment.

Treatments associated with this syndrome are similar to those for other colorectal cancers. (1)

Let: (5)

– surgery, based on colonic resection and lymph node dissection;

– chemotherapy, used in cases of metastatic colon cancer.