Genetic Cancer Syndromes

Question 1

Inheritance and mutation in Li-Fraumeni Syndrome

Answer 1

Autosomal dominant
Germline mutations to p53 tumour suppressor gene

Question 2

What is Li-Fraumeni Syndrome characterised by?

Answer 2

High incidence of malignancies esp. Sarcomas + Leukaemias

Question 3

When is Li-Fraumeni Syndrome diagnosed?

Answer 3

Individual develops sarcoma <45y
OR
1st degree relative diagnosed with any cancer <45y + another family member develops malignancy <45y OR sarcoma at any age

Question 4

On which chromosomes are BRCA 1 and 2 carried?

Answer 4

BRCA 1: Chr 17
BRCA 2: Chr 13

Question 5

What are the risks associated with the BRCA1 and 2 genes?

Answer 5

Breast cancer: 60% risk.
Ovarian cancer: 55% with BRCA 1 + 25% with BRCA 2
Prostate cancer in men with BRCA2

Question 6

Inheritance of Lynch syndrome

Answer 6

Autosomal dominant

Question 7

What characterises Lynch syndrome?

Answer 7

Develop colonic cancer + endometrial cancer at young age
80% will get colonic +/ or endometrial cancer
High risk individuals may be identified using the Amsterdam criteria

Question 8

What is the Amsterdam criteria?

Answer 8

> ,3 family members with a confirmed dx of colorectal cancer, 1 of whom is a 1st degree relative of the other 2.
2 successive affected generations.
,1 colon cancers diagnosed <50y
Familial adenomatous polyposis (FAP) has been excluded.

Question 9

What is Gardners syndrome?

Answer 9

Variant of familial adenomatous polyposis coli
Multiple colonic polyps

Question 10

What extra-colonic disease are seen in Gardners syndrome?

Answer 10

Skull osteoma
Thyroid cancer
Epidermoid cysts
Desmoid tumours

Question 11

Describe inheritance and mutations in Gardners syndrome

Answer 11

Autosomal dominant
Mutation of APC gene on Chr 5

Question 12

Describe management of Gardners syndrome

Answer 12

Due to colonic polyps most undergo colectomy to reduce risk of colorectal cancer