Genetics - Inherited cancers

Question 1

Are inherited cancers germline or somatic mutations?

Answer 1

Germline. They’re present in the egg/sperm and are heritable.

Somatic are non-heritable

Question 2

What are the 3 gene types involved in cancers?

Answer 2

Oncogenes
Tumour Suppressor Genes
DNA mismatch genes

Mainly the last 2 in heritable cancers

Question 3

What do each of the 3 gene types do?

Answer 3

Oncogenes regulate growth
Tumor suppressor genes prevent mutations
DNA mismatch repair genes repair base pair mismatches

Question 4

How does a germline mutation start?

Answer 4

Founder gets the mutation in their egg or sperm –> Ends up in every cell in their offspring.

2nd generation has it in every cell so 50/50 chance of passing it on in their egg/sperm and so on

Question 5

What type of gene is mutated in HNPCC (lynch syndrome)?

Answer 5

Mismatch repair genes

Question 6

How do we clinically spot HNPCC?

Answer 6

Early CRC diagnosis (~45 yrs) predominates in proximal colon

Question 7

What types of cancer are you at risk of with the BRCA1/2 genes?

Answer 7

60-80% get primary breast cancer
40-60% get a 2nd primary breast cancer
20-50% get ovarian cancer
Men will get more prostate or breast cancer

Question 8

What features would make us think a cancer patient might have a hereditary cancer syndrome?

Answer 8

2 or more close relatives
Early age onset
Multiple primary tumours
Bilateral or multiple rare cancers
Characteristic patterns e.g. breast & ovarian
Autosomal dominant pattern

Question 9

What is involved in a cancer genetics process?

Answer 9

Obtain a family history
Confirm diagnoses of cancer
Estimate patients risk
Genetic counselling (including testing and interventions)

Question 10

What are the pros of genetic testing?

Answer 10

• Identifies high risk individuals
• Identifies non-carriers in a family
• Allows early detection & prevention
• Can relieve anxiety

Question 11

What are the limitations of genetic testing?

Answer 11

Can’t detect all mutations
Even if -ve still at risk of sporadic cancer
Can cause psychosocial or economic harm
Intervention efficacy is variable

Question 12

What kind of screening can we do on someone at risk of familial breast cancer?

Answer 12

Annual breast exams and annual/2yrly mammographs 5 yrs before the earliest age of onset in the family

Question 13

What kind of screening can we do for someone at risk of familial CRC?

Answer 13

High risk - 2 yrly colonoscopy from 25

Mod risk - colonoscopy at 35 & 55

Question 14

We can do prophylactic surgery for some familial cancer syndromes such as:

Answer 14

Prophylactic mastectomy - reduces breast cancer to 5% in BRCA1 +ve women

Prophylactic Oophorectomy - eliminates ovarian cancer but peritoneal carcinomatosis can still occur. Also requires HRT till 50.