Genetics and surgical disease

Question 1

Li-Fraumeni Syndrome

Answer 1

Autosomal dominant
Consists of germline mutations to p53 tumour suppressor gene
High incidence of malignancies particularly sarcomas and leukaemias
Diagnosed when:
- Individual develops sarcoma under 45 years
- First degree relative diagnosed with any cancer below age 45 years and another family member develops malignancy under 45 years or sarcoma at any age

Question 2

BRCA 1 and 2

Answer 2

Carried on chromosome 17 (BRCA 1) and Chromosome 13 (BRCA 2)
Linked to developing breast cancer (60%) risk.
Associated risk of developing ovarian cancer (55% with BRCA 1 and 25% with BRCA 2)

Question 3

Lynch Syndrome

Answer 3

Autosomal dominant
Develop colonic cancer and endometrial cancer at young age
80% of affected individuals will get colonic and/ or endometrial cancer
High risk individuals may be identified using the Amsterdam criteria

Question 4

Amsterdam criteria

Answer 4

Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two.
Two successive affected generations.
One or more colon cancers diagnosed under age 50 years.
Familial adenomatous polyposis (FAP) has been excluded.

Question 5

Gardners syndrome

Answer 5

Autosomal dominant familial colorectal polyposis
Multiple colonic polyps
Extra colonic diseases include: skull osteoma, thyroid cancer and epidermoid cysts
Desmoid tumours are seen in 15%
Mutation of APC gene located on chromosome 5
Due to colonic polyps most patients will undergo colectomy to reduce risk of colorectal cancer
Now considered a variant of familial adenomatous polyposis coli