General information

The HNPCC syndrome is based on a genetic change (mutation) in the hereditary information. The nucleus of every human body cell contains 23 pairs of chromosomes. The carriers of the hereditary factors (genes) are lined up on these chromosomes. One of the chromosomes comes from the father and the other from the mother. Each gene is therefore present twice in each cell. If one of the two genes is changed, this is sufficient for the development of the disease (autosomal dominant inheritance).

In HNPCC, in most cases there is a genetic change (mutation) in one of the DNA repair genes (DNA mismatch repair genes). If this altered gene is passed on to one of the children either from the mother or from the father, then this child is a carrier of the mutation that causes HNPCC. The modification of a DNA repair gene means that faulty developments in the development of a cell cannot be repaired and this defective cell grows uncontrollably, i.e. cancer develops. The affected person is at risk of developing malignant tumors of the stomach, small intestine, large intestine, renal pelvis, ureters, mucous membrane of the uterus, ovaries, skin and brain.

HNPCC-typical symptoms do not occur. If cancer develops in the small or large intestine, the symptoms of hereditary cancer are no different from those of spontaneously occurring colon cancer. General symptoms such as tiredness, exhaustion, weight loss, abdominal pain, constipation or diarrhea, blood deposits in the stool and anemia can occur, but can indicate an advanced stage of the cancer.

HNPCC is suspected if cancer in one of the organs mentioned occurs at a very young age (before the age of 50), two cancers from the HNPCC spectrum have occurred simultaneously or one after the other, or in a family also first-degree relatives (parents, siblings, children) of the patient with cancer are ill.

If HNPCC syndrome is suspected, changes in the DNA mismatch repair genes can be looked for. First, tumor tissue is examined to determine whether the proteins that must be present in a cell are actually present. When HNPCC is present, one or more proteins in the cell may be missing. If not all proteins can be detected, a microsatellite stability analysis is performed on the tumor tissue. If there is a change here (microsatellite instability), there is an urgent suspicion of HNPCC.

A mutation analysis (search for a change in a gene) is carried out on a blood sample from the patient. Changes in the genes MLH1 and MSH2 are detected most frequently, less frequently in the genes MSH6 and PMS2. If there is a mutation in one of these genes, the diagnosis of HNPCC is assured.

Therapy for the genetic changes in HNPCC is not possible. If a tumor from the spectrum of tumors caused by HNPCC occurs, it is surgically removed. If metastases are detected, additional treatments (immunotherapy, chemotherapy, radiation) are required.

Recommended check-ups in addition to the individual tumor check-ups (according to the current recommendations of the German Consortium "Familial Colon Cancer"):

From the age of 25 every 12 – 24 months:

•  Physical exam with rectal digital exam
•  Colonoscopy with endoscopy of the terminal ileum
•  Optional abdominal ultrasonography

From the age of 25 every 12 – 36 months:

•  Esophagogastroduodenoscopy

From 30 – 35 years optional:

•  Performing a transvaginal sonography and an endometrial biopsy

Find out about the optional hysterectomy after family planning is complete.

If an HNPCC syndrome has been detected in a cancer patient, there is the possibility of predictive diagnostics (predictive mutation testing) for his relatives. This examination can be carried out after the person has reached the age of majority, after genetic counseling has taken place and with the written consent of the person concerned.

If the mutation known in the family is detected, this relative is a mutation carrier. In this case, the check-ups mentioned are urgently recommended from the age of 25 or 35. The progression of a tumour, which e.g. has developed unnoticed in an intestinal polyp and has not yet caused any symptoms, can be prevented by simply removing the polyp or a suspicious mucosal change.

If the mutation known in the family is not detected in a relative, then he is not a carrier for HNPCC and does not require intensive preventive examinations.

Only members of a family who carry the disease-causing genetic change can pass it on to their children (autosomal dominant inheritance, i.e. each child of the carrier has a 50% risk of inheriting the HNPCC trait). The children of relatives in whom the mutation could not be detected are not at risk for HNPCC.

Research projects of the HNPCC group:

• Participation in the joint project "Familial Colon Cancer" of the German Cancer Aid ("Deutsche Krebshilfe")
• Department of Applied Tumor Biology at the Institute of Pathology Heidelberg