Familial Cancer Syndromes

Question 1

What is the proportion of people who will get cancer? What proportion will die?

Answer 1

1/3 …. 1/4 will die

Question 2

What do gatekeeper cells do (basic)?

Answer 2

Monitor and control mutation and cell death, prevent accumulating mutations

Question 3

What do caretaker cells do (basic) ?

Answer 3

Improve the genomic stability, repair mutations

Question 4

Landscaper cells do what?

Answer 4

Control the stromal environment

Question 5

% chance of cancer with gatekeeper faults?

Answer 5

> 95%`

Question 6

% chance of cancer with caretaker faults?

Answer 6

70%

Question 7

% chance of cancer with landscaper faults?

Answer 7

10-20%

Question 8

Sporadic defects have a high chance of turning to cancer, true or false?

Answer 8

False low rate ~5%

Question 9

Loss of function of tumour suppressor genes does what?

Answer 9

Increases risk of certain cancers eg BRCA1

Question 10

Oncogenes gaining function or mutation does what?

Answer 10

Increases risk of cancers Growth factors etc

Question 11

Classic example of two hit hypothesis?

Answer 11

Retinoblastoma

Question 12

How many tumour suppressor genes must be knocked out on each allele in order to create malignancy? (what type of malignancy)

Answer 12

Both genes on both alleles (sporadic cancers)

Question 13

Inherited cancers are different in the way the tumour suppressor genes are organised, how?

Answer 13

One allele is already knocked out only need one more hit

Question 14

Most cancer syndromes show what type of inheritance|?

Answer 14

Autosomal dominant 50/50

Question 15

A few cancers are autosomal recessive give three examples!

Answer 15

MYH polyposis
Fanconi anaemia
Ataxi telangiectasia

Question 16

What is the proportion of children to inherit a recessive cancer ?

Answer 16

1/4

Question 17

Recessive cancers are often sporadic too, why?

Answer 17

Possible generation skipping

Question 18

How many generations at least do you take in a history?

Answer 18

3

Question 19

Onset at a younger age and multiple primary tumours is classic of what?

Answer 19

Familial cancers

Question 20

Irradiation for Retinoblastoma can increase the risk of what cancer?

Answer 20

Osteosarcoma

Question 21

Bilateral cases of Retinoblastoma are almost always due to what?

Answer 21

Germline mutations

Question 22

Familial Adenomatous polyposis is inherited how?

Answer 22

Autosomal dominant

Question 23

Is FAP high risk if untreated?

Answer 23

Yes ~100% will get cancer if untreated

Question 24

Other features of FAP can include what?

Answer 24

CHRPE, Desmoid tumours and osteomas

Question 25

What is the risk of bowel cancers in hereditary non polyposis colorectal cancer? and when?

Answer 25

60-80% mid 20’s onwards

Question 26

HNPCC is associated with which genes?

Answer 26

Mismatch repair

Question 27

Which criteria is used to diagnose HNPCC?

Answer 27

Amsterdam

Question 28

When should patient with HNPCC start bowel surveillance?

Answer 28

from age 25 every 1-2 years

Question 29

Women with HNPCC might consider what?

Answer 29

Hysterectomy +- BSO

Question 30

What are BRCA1 and BRCA 2 involved in ?

Answer 30

DNA repair

Question 31

BRCA1 or 2 confers higher ovarian cancer risk?

Answer 31

BRCA1

Question 32

Approx risk of breast cancer with BRCA genes?

Answer 32

80%

Question 33

Breast screening for those with BRCA genes consists of what?

Answer 33

MRI yearly 30-50 and mammography from 40 or post menopause

Question 34

What mutation does Li Fraumeni syndrome affect?

Answer 34

P53 rare

Question 35

Risk of cancer at 40 and lifetime risk?

Answer 35

At 40 is 50% and close to 100% lifetime

Question 36

Li Fraumeni syndrome causes what type of cancers?

Answer 36

Breast sarcoma brain leukaemia

Question 37

Li Fraumeni syndrome is often associated with problems in which age?

Answer 37

Children