Hereditary carcinoma syndromes

Peutz et al. were the first to describe Peutz-Jeghers syndrome, named after them, in 1921 (Sommerhaug 1970). Lynch syndrome was first described by Henry T. Lynch (1928 - 2019) (Blohmer 2023) and FAP by Kurt Elster. More than 50 years ago, Joseph Fraumeni Jr. and Frederick Li first described Li- Fraumeni syndrome, which was named after them (Kratz 2022).

Hereditary carcinoma syndrome refers to a tumor predisposition that is usually inherited in an autosomal dominant manner (Ganten 2002).

Hereditary carcinoma syndromes include:

- Lynch syndrome (HNPCC = non-polypous colon carcinoma)

- Peutz-Jeghers syndrome

- Li- Fraumeni syndrome (Herold 2022)

- Hereditary breast and ovarian cancer syndrome

- Hereditary ovarian carcinoma

- Cowden carcinoma

- Hereditary gastric carcinoma (Ghadimi 2022 / Ganten 2002)

- Lynch syndrome (HNPCC = non-polypous colon carcinoma)

This syndrome is characterized by an increased incidence of colorectal carcinomas. However, carcinomas of the stomach, small intestine, urinary tract and endometrial carcinomas are also observed. This syndrome is associated with germline mutations in several DNA repair genes (Ganten 2002).

It was previously assumed that approx. 5 % of all colorectal carcinomas were caused by Lynch syndrome. However, improvements in diagnostics, particularly panel diagnostics, have shown that the figure is actually around 10%. Lynch syndrome is therefore the most common form of hereditary colorectal cancer (Ghadimi 2022).

- Peutz-Jeghers syndrome

This disease occurs only rarely and, in addition to melanin spots on the lips and fingers, also leads to gastrointestinal polyposis with an increased risk of carcinomas of various organs. Mutations are found in the serine-threonine kinase STK11 on chromosome 19p13.3 (Ganten 2002).

- Li- Fraumeni syndrome

The following tumors occur most frequently in Li- Fraumeni syndrome: soft tissue sarcomas, breast carcinomas, brain tumors, bone sarcomas. The germline mutations are found in the tumor suppressor gene p53 (Ganten 2002).

- Hereditary breast and ovarian cancer syndrome

This syndrome includes mutations in the BRAC1 gene with carcinomas of the breast, ovaries or tubes or in the BRCA2 gene with carcinomas of the stomach, pancreas, colon, breast carcinoma in men and prostate carcinoma (Knabben 2015).

- Hereditary ovarian cancer

The tumors are located on the ovaries. Other possible causes include neoplasms of the lung, liver, pancreas, skin, kidney, prostate, breast cancer, lymphoma and leukemia. Mutations of the RAD51C gene are found here. (Knabben 2015).

- Cowden carcinoma

The mutation is located on the PTEN gene and can cause thyroid, kidney, endometrial and breast cancer (Knabben 2015).

- Hereditary gastric carcinoma

Patients with germline mutations in the brca- 2 gene on chromosome 13q12.3 have an increased risk of developing gastric carcinoma. They also have an increased risk of pancreatic and prostate carcinomas (Ganten 2002) as well as invasive lobular breast carcinomas and gastric carcinomas (Knabben 2015).

Patients who develop colorectal cancer at the age of 35 or younger should be screened for hereditary carcinoma syndrome (Leiner 2015).

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