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?

Oncogene, Tumor suppressor, DNA Mismatch

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.

Question 15

What are the steps of the Cell Cycle?

Answer 15

G1 - Growth (Oncogene mediated)
G0 - Rest
S - Synthesis (Tumour Suppressor mediated)
G2 - Repaired (DNA Repair gene mediated)
M - Mitosis

Question 16

What kind of gene is the Retinoblastoma gene?

Answer 16

Tumour Suppressor Gene

Question 17

What is the main mechanism for familial cancer?

Answer 17

DNA Mismatch Repair fault.

Leads to mutation produced by unrepaired DNA.

Question 18

What is HNPCC?

Answer 18

Hereditary Non Polyposis Colorectal Cancer

More commonly known as Lynch Syndrome.

Question 19

What side of the intestines is most susceptible to Lynch Cancer?

Answer 19

Right-side

Question 20

Colon Cancer is 78% chance risk of occurrence with Lynch. What is Endometrial cancer percentage?

Answer 20

50%

Question 21

What are the risk percentages with BRCA1 and 2 Cancers?

Answer 21

Breast cancer - 60%

Secondary Primary Breast Cancer - 40% to 60%

Ovarian Cancer - 20% to 50%

Question 22

When do we suspect Lynch Syndrome?

Answer 22

• Cancer in 2 or more close relatives.
• Early Age Diagnosis
• Multiple Primary Tumours
• Bilateral / Multiple rare cancers
• Characteristic pattern of tumours (i.e. breast and ovary)
• Evidence of autosomal dominant transmission

Question 23

What are the steps of a Genetics consultation with someone with anyone at risk of cancer?

Answer 23

1) Family Hx
2) Risk Estimation
3) Explanation of basis of risk
4) Intervention
5) Genetic Testing (Consider in high risk patients)

Question 24

What interventions can be given to people with familiar cancer risk?

Answer 24

Increased awareness of symptoms / signs

Lifestyle changes (diet, smoking and excercise)

Prevention (aspirin and oestrogen use)

Screening

Prophylactic Surgery

Question 25

What are the surveillance options for Breast Cancer families?

Answer 25

X-ray
Mamography

5 years before the youngest cancer.