Week 2 - Inherited pre-disposition to cancer

Question 1

What is the percentage of cancers that are associated with a genetic pre-disposition?

Answer 1

4%

Question 2

Name 3 key characteristics of cancers with inherited pre-disposition?

Answer 2

1. Family history of (same) cancer
2. Early age of onset, especially childhood
3. Multiple cancers in one individual
4. High occurrence of rare cancer
5. Premalignant conditions, e.g. polyps

Question 3

What is the definition of a Cancer Predisposition Gene?

Answer 3

Genes in which rare mutations confer >2x relative risk
of cancer, and at least 5% of individuals with relevant mutations
develop cancer

Question 4

How many cancer pre-disposition genes are currently known?

Answer 4

114

Question 5

What is the prevelance of Retinoblastoma?

Answer 5

1 in 20,000 children - 80 case/year

Question 6

What is the average age of Retinoblastoma presentation?

Answer 6

90% present before 5 years of age.

Question 7

What is the treatment(s) for retinoblastoma? (2)

Answer 7

Surgery & Radiotherapy

Question 8

What are the two forms of Retinoblastoma and what percentage of cases do they represent?

Answer 8

Sporadic - 60%

Familial - 30%

Question 9

What gene is mutated in Retinoblastoma and what type of gene is it?

Answer 9

RB1 - Tumour Suppressor Gene

Question 10

What type of trait is pre-disposition inherited as?

Answer 10

Dominant

Question 11

What is an obligate carrier?

Answer 11

A genetic carrier of a mutation but does not show any signs of the condition.

Question 12

What is Li-Fraumeni Syndrome?

Answer 12

A very rare autosomal dominant genetic disorder that pre-disposes carriers to cancer development.

Question 13

What is the diagnostic criteria for Li-Fraumeni Syndrome?

Answer 13

Diagnostic criteria:

1. Individual <45 years with sarcoma
2. 1st degree relative with any cancer <45 years
3. Another 1st (or a 2nd) degree relative with any cancer <45yo or sarcoma at any age

Question 14

What gene does Li-Fraumeni mutate to develop its cancer causing properties?

Answer 14

TP53

Question 15

What does MEN2 stand for?

Answer 15

Multiple Endocrine Neoplasia (MEN2)

Question 16

How is MEN2 inherited?

Answer 16

Autosomal Dominant

Question 17

What is the treatment for MEN2?

Answer 17

Surgery

Question 18

What cancers does MEN2 cause?

Answer 18

Medullary thyroid carcinoma,
parathyroid carcinoma, pheochromocytoma
(adrenal gland)

Question 19

What percentage of breast cancer is hereditary?

Answer 19

5-10% of breast cancer

Question 20

What is the difference between BRCA1 and BRCA2 with regards to their ability to increase the risk of other cancers and which cancers are they?

Answer 20

BRCA2 - Increased risk of: pancreas, fallopian tubes, stomach, (prostate)

Question 21

What are the 3 clinical implications of identifying mutations?

Answer 21

1. Prevention:
   - prophylactic surgery
   - chemoprevention
   - screening
2. Aid diagnosis & management
   - extent of surgery
   - platinum therapy

3.Provide information
-why the cancer occurred
-evaluate risk for family
member