Genetics - Cancer

Question 1

What proportion of breast cancer is hereditary?

Answer 1

5-10% hereditary

15-20% Family clusters

Question 2

What proportion of ovarian cancer is hereditary?

Answer 2

5-10%

Question 3

What are the causes of colorectal cancer?

Answer 3

Sporadic 65%
Familial 10-30%
Lynch syndrome/HNPCC 5%
FAP 1%

Question 4

What mutations cause cancer?

Answer 4

Germline (heritable)

Somatic (sporadic)

Question 5

What are germline mutations?

Answer 5

Inherited from single alteration in zygote

Question 6

What oncogene is associated with Leukaemia?

Answer 6

ABL

BCR-ABL Fusion Protein

Question 7

How many oncogene mutations are required for cancer growth?

Answer 7

1

Question 8

How many Tumour suppressor gene mutations are required for cancer growth?

Answer 8

1 - carrier

2nd or loss - cancer

Question 9

What is the main mechanism of familial cancer?

Answer 9

Faulty DNA mismatch Repair

Question 10

What is the cause of Lynch syndrome/HNPCC?

Answer 10

Mutation is mismatch repair genes

Question 11

How does HNPCC present?

Answer 11

Colorectal polyps/adenomas

Question 12

What is the normal function of oncogenes?

Answer 12

Regulate cell growth

Question 13

HNPCC/Lynch increases the risk of what?

Answer 13

Cancer - Colorectal
Endometrial
Urinary tract
Ovarian

Question 14

BCRA 1 and 2 increase lifetime risk of what cancers?

Answer 14

Breast (60-80%)
Second primary Breast (40-60%)
Ovarian cancer (20-50)

Question 15

BRCA 2 increases the risk of what cancers in males?

Answer 15

Prostate cancer

Breast cancer

Question 16

When should hereditary cancer syndromes be suspected?

Answer 16

Cancer in 2 or more close relatives
Early age diagnosis
Multiple primary tumours
Characteristic patterns

Question 17

Most inherited cancers are inherited in what pattern?

Answer 17

Autosomal dominant

Question 18

What is the cancer genetics process?

Answer 18

Obtain detailed FH - pedigree
Confirmed cancer diagnosis
Risk estimation
Counselling

Question 19

What interventions can be applied to reduce the risk in a high risk patient?

Answer 19

Increased awareness of signs/symptoms
Lifestyle changes
Prevention
Screening
Prophylactic surgery

Question 20

What are the breast cancer surveillance options?

Answer 20

Begin 5yr under age of 1st cancer in family
Annual breast exams
Mammogram (18 monthly for high risk)

Question 21

What is the incidence of breast cancer in BRCA 1+ve women post-prophylactic mastectomy?

Answer 21

5%

Question 22

What are the colonoscopy recommendations in CRC families?

Answer 22

Gene carrier 2yearly from 25

Prophylactic aspirin

Question 23

What genetic tests are used for Lynch syndrome?

Answer 23

Immuno-histochemistry for microsatellite instability

Need 2 somatic hits

Question 24

What are the benefits of genetic testing for cancer?

Answer 24

Identify high risk
Identifies non-carriers
Allows early detection
May relieve anxiety

Question 25

What are the limitations of genetic testing for cancer?

Answer 25

Does not detect all mutations
Continued risk of sporadic caner
Psychosocial/economic harm

Question 26

When do you refer a patient to genetic counselling if their parent had cancer?

Answer 26

If the parent was diagnosed <40y/o