Hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colon cancer non- ( correct name actually: Hereditary non- polyposis colorectal cancer -associated ) ( HNPCC) or Lynch syndrome is a hereditary nonpolyposis colorectal cancer form, that is, without the occurrence of many polyps in the colon, the autosomal dominant is inherited.

• 5.1 Lynch syndrome type I
• 5.2 Lynch syndrome type II

Epidemiology

Hereditary nonpolyposis colorectal cancer ( HNPCC) is the most common hereditary colon cancer form and affects approximately 5% of colorectal cancer cases. At about 75 % of colon cancer gene carriers occurs. The mean age at diagnosis is 45 years.

Children of patients according to the mode of inheritance a probability of 50 % to be gene carriers.

Pathophysiology and Pathology

Usually it comes in the hereditary nonpolyposis colon cancer ( HNPCC) the occurrence of multiple malignant colon tumors either synchronously (simultaneously) or metachronous ( staggered ). The tumors are localized in the proximal colon ( right-sided colon and cecum ) in more than two thirds of cases. In addition to the occurrence of colon cancer occurs in women over the average frequency in the occurrence of endometrial cancer ( uterine cancer) (cumulative risk up to age 70 about 20%, according to other sources 40 % - 60%). Furthermore, there is a family clustering of cases of gastric cancer ( 6%), cancer of the small intestine (1%), liver cancer and bile duct cancer ( 4% ), cancer of the urinary tract (2%), ovarian cancer ( 1-3 %) and pancreatic cancer ( 2% ), skin cancer ( 2%) and brain tumors ( 3%, mostly glioblastoma ) and Talgdrüsenadenome and keratoacanthomas ( in Muir -Torre syndrome).

Molecular biology of hereditary non -polyposis cancer

Characteristically, are changes in the microsatellite markers detected by molecular methods in those affected. In patients with hereditary non -polyposis cancer is found inside of an affected individual have a sequence length difference between tumor and healthy tissue as an indication of a faulty DNA replication. This phenomenon is as microsatellite instability.

Meanwhile, six genes are known whose germline mutation can lead to a hereditary non -polyposis cancer occurrence: hMSH2 ( 31%), hMLH1 ( 33%), hPMS1 (2%), hPMS2 ( 4%), hMSH6 and hMLH3. These genes encode proteins from the group of so-called DNA mismatch repair proteins whose task it is to identify possible errors in the replication of DNA during the cell division and eliminate them. Type 8 of the syndrome is caused by a deletion of several exons of the EpCAM gene MSH2 above and subsequent epigenetic gene silencing of MSH2.

Diagnostic criteria

Amsterdam I criteria

All criteria must be met.

Amsterdam II criteria

All criteria must be met.

Revised Bethesda criteria

At least one criterion must be met.

Tumors of patients should be examined for the presence of microsatellite instability in the following cases:

(*) To the HNPCC - associated tumors include tumors: colorectal, endometrial, stomach, ovarian, pancreas, ureter or renal pelvis, biliary tract, small intestine and brain (usually glioblastoma as Turcot syndrome ) and Talgdrüsenadenome and keratoacanthomas ( in Muir -Torre syndrome)

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

Inheritance pattern

There are two patterns of inheritance.

Lynch syndrome type I

In these families, passed from generation to generation almost exclusively on colon cancer.

Lynch syndrome type II

In these families, in addition to colon cancer especially uterine and ovarian cancer is detected, as well as cancer of kidney, liver, stomach, small intestine.

Screening program for pre-and after-care

From the project " familial colorectal cancer " a lifelong screening program for HNPCC patients is recommended:

Once a year, in addition to other follow-ups such as blood tests, fecal occult blood, chest:

For family members in the same lineage annual survey recommendations apply to the care, unless, at the molecular genetic level it was demonstrated that the genetic defect was not inherited. The beginning of the investigations is recommended from the age of 25, but not later than 5 years before the occurred first in the family case (eg: recent sufferers in the family was at the onset of the disease 25 years old, then you should check-ups for all family members with the latest the age of 20 start ).