Genetic Predisposition to Cancer

Question 1

From what types of mutations can cancer arise?

Answer 1

Somatic mutations (non-inheritable)
Germline mutations (egg/sperm; passed on; every cell in child)

Question 2

What three types of genes can cause cancer?

Answer 2

Oncogenes

Tumour suppressor genes

DNA damage-response genes

Question 3

How can oncogenes cause cancer?

Answer 3

• formed from proto-oncogenes
• accelerate cell division
• one mutation needed to lead to cancer

Question 4

What is the function of proto-oncogenes?

Answer 4

Regulation of cell growth and differentiation

Question 5

Give an example of an oncogene and a cancer it can cause

Answer 5

RET can lead to multiple endocrine neoplasia

Question 6

What is the function of tumour suppressor genes?

Answer 6

• inhibit the cell cycle
• promote apoptosis
• mutations in both needed to lead to cancer (‘two-hit hypothesis’)

Question 7

Give an example of a tumour suppressor gene and a cancer it can cause when defective

Answer 7

BRCA1 can lead to breast cancer

APC can lead to FAP

Question 8

What is HNPCC?

Answer 8

Hereditary non-polyposis colorectal cancer

Question 9

What is microsatellite instability?

Answer 9

Phenotype of DNA damage-response genes:

Microsatellite DNA fragments can be detected using PCR and indicate MMR isn’t working properly

Question 10

What is the function of DNA damage response genes?

Answer 10

• repair of DNA errors (during replication/synthesis…)

- mutations in both needed to lead to cancer

Question 11

What is another name of DNA damage response genes?

Answer 11

MMR - mismatch repair genes

Question 12

Give an example of a MMR/DNA damage-response gene and a cancer it can cause when defective

Answer 12

MLH1 can lead to HNPCC

Question 13

Give two other possible genetic causes of cancer

Answer 13

• autosomal recessive disorders (e.g. MYH associated polyposis/MAP)
• multiple modifier genes of lower genetic risk

Question 14

What are the features of heritable retinoblastoma?

Answer 14

• bilateral tumours
• 20% family history
• diagnosis at < 1 year old
• every cell has the mutation, therefore increased risk of osteosarcoma/melanoma

Question 15

What are the features of non-heritable retinoblastoma?

Answer 15

• unilateral tumour
• no family history
• diagnosis at around 2 years old
• no increased risk of second primary cancers

Question 16

Give some environmental risks of developing breast cancer

Answer 16

• ageing
• diet
• exercise
• family history…

Question 17

Mutations in what genes can cause breast cancer?

Answer 17

• BRCA1
• BRCA2
• PTEN
• TP53
• many undiscovered genes

Question 18

What is the normal function of BRCA1?

Answer 18

Codes for a tumour suppressor protein that repairs damaged DNA (example of a tumour suppressor gene)

Question 19

What is the normal function of BRCA2?

Answer 19

DNA repair by homologous recombination

Question 20

Give some risks of developing colorectal cancer (CRC)?

Answer 20

• ageing
• history of CRC/adenomas
• IBS
• high fat/low fibre diets

Question 21

Name three types of colorectal polyposis

Answer 21

FAP (familial adenomatous polyposis)
AFAP (attenuated FAP)
MAP (MYH associated)

Question 22

What are the clinical features of HNPCC?

Answer 22

• early diagnosis age
• tumours throughout colon
• extracolonic cancers also present

Question 23

What are the clinical features of FAP?

Answer 23

• high penetrance for adenomas
• extracolonic cancers
• CHRPE often present
• untreated polyposis leads to a 100% chance of developing cancer

Question 24

What are the clinical features of AFAP?

Answer 24

• later onset
• few adenomas
• no CHRPE present
• upper GI lesions
• associated with mutations in the APC gene

Question 25

What is CHRPE?

Answer 25

Congenital hypertrophy of the retinal pigment epithelium