Hereditary non-polyposis colorectal cancer

from Wikipedia, the free encyclopedia
Classification according to ICD-10
C18.9 Malignant neoplasm: colon, unspecified
Z80.0 A family history of malignant neoplasm of the digestive organs
ICD-10 online (WHO version 2019)

The hereditary non-polyposis colon cancer (correct name actually: hereditary non-polyposis colorectal cancer-associated) ( HNPCC ) is an inherited colon cancer form without polyposis, d. H. without the appearance of many polyps in the intestine. However, it is inconsistent in the nomenclature whether HNPCC only refers to cases with a proven mutation in one of the known HNPCC-associated genes (classic Lynch syndrome ), or also hereditary forms of colon cancer with the same or a similar appearance, but so far unclear cause. The latter are therefore sometimes summarized under the term familial colorectal cancer type X (FCCTX). Not to be confused with the HNPCC is familial adenomatous polyposis (FAP), a hereditary form of colon cancer with an abundance of polyps.

Epidemiology

Hereditary colon cancer without polyposis (HNPCC) is the most common hereditary form of colon cancer and affects around three percent of colon cancer cases. Its prevalence in the general population is around 1 in 300 to 500, making it the most common cancer predisposition.

root cause

The autosomal dominant inheritance

In the meantime 5 genes ( MSH2, MSH6, MLH1, PMS2 , and EPCAM ) are known which, if a pathogenic mutation is present, can lead to the occurrence of a hereditary non-polypous carcinoma. These genes code for proteins from the group of so-called DNA mismatch repair proteins , whose task it is to identify and eliminate possible errors in the replication of the DNA during cell division. The exception to this is EPCAM , which can influence its expression due to its location directly in front of MSH2 . The inheritance is autosomal dominant, which means that those affected have a 50% probability of passing the disease on to their children regardless of gender and that the disease is very likely to be manifested with only one affected allele .

In addition, two more genes have now been identified, TGFBR2 and MLH3 , the loss of function of which causes HNPCC types 6 and 7. In contrast to the classic HNPCC types, tumors of this etiology do not seem to be associated with microsatellite instability , which indicates a different pathomechanism. In addition, because the number of cases so far is too low, it has not been clarified how penetrative pathogenic variants of these genes are, apparently the disease occurs with a lower probability and at a rather older age. However, the penetrance also varies within the classic HNPCC genes: Mutations in the MLH1 and MSH2 genes impair DNA repair more than mutations in MSH6 and PMS2 and are therefore considered to be high-risk genes .

Tumor spectrum

Microfoto of colon cancer with lymphocytes in the tumor, as is often the case with HNPCC. HE staining .

In general, people diagnosed with HNPCC have an increased lifetime risk of various cancers and the like. a. of the large intestine, stomach, urogenital tract, small intestine, biliary tract, CNS and skin. In addition, female individuals have a significantly increased lifetime risk of endometrial and ovarian cancer. The exact lifetime risk, however, depends on the underlying genetic defect.

A variant of the HNPCC is the Muir-Torre syndrome (MRTES), in which sebum adenomas and keratoacanthomas also occur.

Molecular biology of hereditary non-polypous carcinoma

Characteristically, changes in microsatellite markers are detected in those affected using molecular biological methods. In patients with a hereditary non-polypous carcinoma, a sequence length difference between tumor and healthy tissue is found within an affected individual as an indication of defective DNA replication . This phenomenon is known as microsatellite instability . However, this does not occur in all forms (see above).

Diagnostic criteria

Amsterdam II criteria

All criteria must be met.

  1. at least three family members with HNPCC-associated carcinoma (colon / rectum, endometrium, small intestine, renal pelvis / ureter)
  2. one of them first-degree relatives of the other two
  3. Diseases in at least two consecutive generations
  4. at least one patient with a diagnosis of cancer before the age of 50
  5. Exclusion of FAP ( familial adenomatous polyposis )

Revised Bethesda Criteria

At least one criterion must be met.

Patients' tumors should be examined for microsatellite instability in the following cases:

  1. Patients with colorectal cancer before the age of 50.
  2. Patients with synchronous or metachronic colorectal cancer or other HNPCC-associated tumors (*), regardless of age.
  3. Colorectal cancer patients with MSI-H histology (**) before the age of 60.
  4. A patient with colorectal cancer (regardless of age) who has a 1st degree relative with a colorectal cancer or an HNPCC-associated tumor before the age of 50.
  5. A patient with colorectal cancer (regardless of age) who has at least two 1st or 2nd degree relatives who have been diagnosed with colorectal cancer or an HNPCC-associated tumor (regardless of age).

(*) HNPCC-associated tumors include tumors in: colorectum , endometrium , stomach , ovaries , pancreas , ureter or renal pelvis , bile duct , small intestine and brain (mostly glioblastomas as in Turcot's syndrome ) as well as sebum adenomas and keratoacanthomas (in Muir- Torre Syndrome )

(**) Presence of tumor-infiltrating lymphocytes , Crohn- like lymphocytic reaction, mucinous / signet ring differentiation, or medullary growth pattern

Early detection program for pre- and aftercare

The joint project "Familial Colon Cancer" recommends a lifelong early detection program for HNPCC patients:

Once a year in addition to the other aftercare such as blood tests, occult blood in the stool, chest:

  1. Physical examination
  2. Abdominal ultrasound
  3. Complete colonoscopy
  4. Gynecological examination for endometrial and ovarian cancer (including transvaginal sonography and Pipelle endometrial biopsy)
  5. Gastroduodenoscopy (from the age of 35)

The same annual check-up recommendations apply to first-degree family members as a precaution, unless it has been proven at the molecular genetic level that the genetic defect was not inherited. It is recommended to start the examinations from the age of 25, but at the latest 5 years before the case that first occurred in the family (e.g. the youngest affected person in the family was 25 years old when the disease occurred, then preventive medical examinations for all family members should be included at the latest start at the age of 20).

Individual evidence

  1. ↑ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119982/
  2. ^ Lynch Syndrome - Associated Colorectal Cancer. In: NEJM.org. Retrieved December 30, 2018 .
  3. Jump up ↑ Robert J. MacInnis, John L. Hopper, Polly A. Newcomb, Noralane M. Lindor, Yingye Zheng: Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer . In: Cancer Epidemiology and Prevention Biomarkers . tape 26 , no. 3 , March 1, 2017, ISSN  1538-7755 , p. 404-412 , doi : 10.1158 / 1055-9965.EPI-16-0693 , PMID 27799157 , PMC 5336409 (free full text) - ( aacrjournals.org [accessed December 30, 2018]).
  4. ↑ https://www.mgz-muenchen.de/files/mgz/Download/Diagnostische%20Schwerpunkte/Gastrointestinale%20Tumor Krankungen%20(Uebersichtkarte) .pdf
  5. ↑ Verena Steinke, Christoph Engel, Reinhard Büttner, Hans Konrad Schackert, Wolff H Schmiegel: Hereditary Nonpolyposis Colorectal Cancer (HNPCC) / Lynch Syndrome . In: Deutsches Ärzteblatt International . tape 110 , no. 3 , January 2013, ISSN  1866-0452 , p. 32–38 , doi : 10.3238 / arztebl.2013.0032 , PMID 23413378 , PMC 3566622 (free full text).
  6. ↑ https://www.omim.org/entry/614331
  7. ↑ https://www.omim.org/entry/614385
  8. ↑ https://www.aerzteblatt.de/archiv/134013/Erblicher-Darmkrebs-ohne-Polyposis
  9. ↑ Joint project "Familial colon cancer" of the German Cancer Aid
  10. ^ R. Schneider et al.: The Lynch Syndrome - Epidemiology, Clinic, Genetics, Screening, Therapy. In: Journal of Gastroenterology. 2012; 50, pp. 217-225.
  11. ↑ W. Schmiegel et al .: S3 guideline "Colorectal carcinoma". In: Journal of Gastroenterology. 2008, 46, pp. 1–73 (archive link ( memento of the original dated December 29, 2009 in the Internet Archive ) Info: The archive link has been inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. ) @1@ 2Template: Webachiv / IABot / www.dgvs.de

See also

Web links