Genetically induced colorectal cancer

Colorectal cancer is one of the most common cancer types in Germany. The cause is usually unclear. Three to five percent of all cases can be attributed to known gene changes, which can be inherited and, above all, cause colorectal cancer. Those affected have a very high risk of becoming young. However, there are effective screening programs.

According to the data of the Center for Cancer Registry Data at the Robert Koch Institute (RKI), between 62,000 and 64,000 people in Germany annually develop cancer of the colon and rectum. In addition, there are several thousand cases in which cancer early stages are detected. (1) The focus of attention is clearly on the advanced age. More than half of those affected are over 70 years old at the time of the diagnosis, only one in ten is younger than 55 years. (1)

Often discovered too late

However, this does not apply to people who are affected by hereditary colorectal cancer. They have specific mutations in individual genes that have important functions in the control of the cell cycle and the repair of genetic damage (DNA damage). These gene defects are passed on to the germ line and lead to the fact that early metabolic processes in the tissue take place, and those affected most often develop colorectal cancer at an unusually young age – approximately between 20 and 40 years of age. (2,3)

Since screening programs such as tests on blood in the stool or colonoscopy are offered as standard only from the age of 50 and 55, they are usually too late for these patients. It is therefore all the more important to look at criteria that can indicate the presence of a hereditary colorectal cancer form.

How do I recognize my risk?

For a personal danger speaks, if close relatives already had colorectal cancer and the illness at least occurred in one case early (before the 50th Lebensjahr). Even if a family member is diagnosed with colorectal cancer several times in the course of his life or in the family, other cancer diseases such as stomach cancer , uterine mucous cancers or a brain tumor can be noted. This may indicate a hereditary tumor syndrome, Prof. Stefan Aretz, senior physician and specialist for human genetics At the Center for Family Colorectal Cancer and the Center for Hereditary Tumor Diseases of the Bonn University Hospital. A gene change in the germ line can affect all body cells, which is why cancer in other organs is always possible in affected families. (2,4)

HNPCC and FAP are the most common forms

Depending on which particular gene mutation is present in a family, different hereditary colon cancer forms or also tumor syndromes are shown. In principle, a distinction is made between forms of hereditary colorectal cancer without polyposis (hereditary non-polypoid colorectal carcinoma , abbreviated HNPCC or also Lynch syndrome) and hereditary polyposis syndromes.

Nearly all forms of colorectal cancer, including HNPCC, develop on the basis of polyps, that is benign intestinal tumors,” says Aretz. However, polyposis syndromes are associated with the appearance of unusually many polyps in the intestine. In the most common form, classical familial adenomatous polyposis (FAP), which is also the second most common hereditary colorectal cancer form behind HNPCC, sufferers usually develop first polyps in the teenagers’ mouth; Later hundreds to thousands can occur. (5) In the case of hereditary colorectal cancer without polyposis (HNPCC), there is no significantly increased number of intestinal polyps. According to Aretz, however, this gene mutation leads to the fact that the period of cancer development from the polypes is shortened.

High risk of colorectal cancer

People with such genetic defects therefore have a very high risk of developing colorectal cancer during their lifetime, but also of other tumors. According to current surveys, up to 70% of all affected people develop colorectal cancer, up to 50% of uterine cancer , up to 8% of ovarian cancer and up to 5% of stomach cancer . (6) Up to 2% of HNPCC sufferers are infected with CNS tumors (brain and spinal cord tumors). (5, 6) carriers of the FAP mutation have a nearly 100% colorectal cancer risk. This means that they will develop colorectal cancer in almost every case without adequate screening and therapy. (5,7)

Every second child of affected parents inherits the gene mutation

The predisposition for a hereditary tumor disease is passed on to the offspring in most known syndromes with 50% probability. Statistically speaking, every second child inheres the risk-bearing heredity from the affected parent. (8,9)

In any case, clarify

If there is a corresponding suspicion, in any case a humanitarian assessment and consultation should be carried out in a qualified center, said Aretz. The specialists there examine the risk for the presence of a hereditary cancer disease and clarify to the further investigations on, for example, possible genetic tests, and their consequences. The counseling also includes a risk assessment for other persons in the family. (8, 9, 10) Corresponding contacts to the centers are listed in the service section below.

Genetic tests ensure diagnosis and help relatives

If the specific familial gene mutation is known by tests with an already affected family member, a predestive genetic test can be offered to relatives. According to Genetic Diagnostics, such a predictive test should always take place within the framework of a humanitarian consultation. (4, 8, 10)

Genetic tests in many cases allow the reliable detection or exclusion of the mutation in a risk-affected person of the affected family. Suppliers can be identified at an early stage and have the opportunity to take special, tight-meshed precautionary measures. (10) “Above all, we are also testing to relieve those who are not plant bearers. It makes no sense to send a child a whole teenager long to colonoscopy, which is not a plant carrier, “says Aretz. In the case of colorectal cancer forms such as HNPCC occurring in the adult age, however, predictive genetic tests are generally carried out only if the patient is at least 18 years old and wants a test. Genetic counseling and testing are always voluntary. Patients should be aware beforehand that the results can be as well as relieving.

Also, genetic testing does not always provide clarity. For a part of hereditary colorectal cancer diseases, the genetic basis is not yet or only insufficiently researched. If the familial colorectal cancer risk can not be determined by genetic tests, the diagnosis is made based on the family history and the specifically occurring cancer diseases (the so-called “tumor spectrum”). (5) It is estimated, however, that a large part of hereditary cancer is not detected at the moment, which means that many risk-takers are not adequately prepared. (8th)

Risks can be effective

Anyone who has a family-related increased colorectal cancer risk should take precautionary measures. The central element of the screening is the annual colonoscopy (colonoscopy). It allows early detection and removal of mucosal growths. In some polyposis forms such as the classic FAP, annual colonoscopy is recommended from the age of 10 to 12, and for HNPCC from 25 years of age. (7.11) According to Aretz, the chances of preventing the occurrence of malignant tumors by early-stage screening programs are great.