Lynch syndrome (HNPCC)

Colorectal Cancer
Colon cancer is a malignant tumor of the colon (large intestine). A tumor develops because one of the cells in our body starts to grow in an uncontrolled manner. Tumors can be benign or malignant. A benign tumor grows by pushing surrounding tissue aside without causing much damage, whereas a malignant tumor (a cancer) invades and often damages surrounding tissue. Malignant tumors in the colon develop from intestinal polyps. A polyp is an abnormal growth projecting from the colonic mucosa, the tissue that covers the inside of the large intestine. Polyps are benign, but as some may change and become malignant over time, all polyps are usually removed.

Hereditary Colorectal Cancer (Lynch Syndrome)
About 3 to 5% of patients with colorectal cancer have a hereditary form known as Lynch syndrome. Hereditary colorectal cancer is usually diagnosed at a younger age (often below the age of 60) and differs in several other ways from the non-hereditary form. Most hereditary colorectal cancers occur on the right side of the large intestine, i.e. in the ascending or transverse part of the colon. Another feature of hereditary tumors is that, following a first colon cancer, a patient has an increased chance of developing a second colon tumor. A final characteristic is that family members in some families with hereditary colon cancer may develop cancer of the uterus and other tumors.

Symptoms
A polyp or a malignant tumor in the colon does not always cause symptoms. If a complaint occurs, the sort of complaint depends on the location of the tumor.

The following symptoms may occur when a polyp or a malignant tumor is located in the last part of the intestine:

changes in stool pattern
diarrhea or alternating constipation and diarrhea
urgency but without feces
blood or mucus in the stool

If a large polyp or malignant tumor has developed in the first section of the colon, the following symptoms may occur:

anemia due to chronic blood loss in the colon
a vague abdominal pain
a swelling in the abdominal area

It is important to realize that these symptoms do not always mean that a polyp or tumor is present! This type of complaint can also have other causes, such as a low-fiber diet or nervousness. A hemorrhoid is a common cause of blood and/or mucus in the stool. However, it is important that you consult your GP or specialist if your symptoms persist for more than three weeks.

Heredity
The body is made up of cells, each of which has a nucleus containing 23 pairs of chromosomes, thus 46 in total. Chromosomes contain tightly packed DNA, parts of which act as genes, the DNA ‘blueprints’ for a hereditary trait. For each of your 23 pairs of chromosomes, one came from your mother and the other from your father, and which chromosome from each pair is inherited is entirely random. From mother and father combined, a child thus receives 46 chromosomes. In hereditary colorectal cancer, predisposition to disease is passed to offspring by a parent. Children, both boys and girls, have a 50% chance of inheriting a chromosome that carries a predisposition for hereditary colon cancer. This, of course, means that there is also a 50% chance that a child will not inherit the predisposition, and will not have an increased risk of disease later in life. However, a child that inherits a chromosome carrying a predisposition to disease is at increased risk, and it is generally believed that the disease rarely skips a generation. Hereditary colon cancer is caused by a defect in a so-called ‘mismatch repair’ gene (examples of which include MSH2, EPCAM, MLH1, MLH2 and PMS2).

Family Study
The question of whether a hereditary form of colorectal cancer occurs in a family can be partly answered by a family study. This investigation involves drawing a family tree that contains medical data from family members. When colon cancer is diagnosed in three or more close relatives, and the disease was diagnosed in at least one person at an age younger than 50 years, a diagnosis of hereditary colorectal cancer is likely. In some families that meet these criteria a gene defect in a mismatch repair gene (MLH1, MSH2, MSH6, and PMS2) will be identified.

Preventive measures for the carriers of one of the gene defect causing Lynch Syndrome
If investigation of the family suggests Lynch syndrome, tests will be carried out by the clinical geneticist on a patient’s DNA. When a gene defect is diagnosed, the patient will be advised to undergo colonoscopy every two years. These examinations usually start between 20 and 25 years of age. Other family members with a high disease risk will be referred by their general practitioner for an appointment at the outpatient clinic with a gastroenterologist, an internist or sometimes a surgeon. In the first interview with one of these specialists, the possibilities for regular preventive procedures will be discussed. This interview also gives the patient the opportunity to talk over any reluctance or fear regarding the medical procedures. A colonoscopy involves introducing a flexible camera tube into the rectum via the anus. This will allow the doctor to carefully examine the mucous membrane of the large intestine. A colonoscopy takes between 15 and 45 minutes, and you will usually receive a sedative and a painkiller. For accurate inspection of the intestinal wall, the intestines must be clean. A patient will therefore be asked to drink one or more liters of water, together with a laxative (usually Moviprep or Picoprep), the day before the examination.

Treatment
When discovered, polyps are removed during a colonoscopy. Most polyps prove to be benign lesions. However, if a malignant tumor is diagnosed, an operation to remove the section of intestine close to the tumor (bowel resection) becomes necessary. In hereditary colon cancer, new polyps and malignant tumors may sometimes develop in the remaining part of the intestine. Removal of the entire colon (total colectomy) is therefore preferred in young patients. During this operation, the last part of the small intestine (the ileum) will be connected to the rectum (the rectum), a surgical technique known as colectomy with ileorectal anastomosis.

Preventive measures on uterine cancer
Uterine cancer may also occur in some families with Lynch syndrome. It is therefore advisable that women in these families participate in uterine cancer screening once every 1 to 2 years, from the age of 40. This preventive examination usually consists of a physical examination by a gynecologist, and a transvaginal ultrasound, a technique that uses sound waves, via the vagina, to create an image of the uterus and ovaries.