Familial cancer syndromes

Question 1

List the lifetime risk of ovarian cancer based on number of relatives with ovarian cancer

Answer 1

Life time risk 1.4%
1 relative with ovarian cancer - 5% if 1st degree
2 relatives with ovarian cancer - 15% if 1st degree
Familial ovarian cancer syndrome - 30-50%

Question 2

In what scenario do women need testing for BRCA mutation?

Answer 2

• One 1st degree relative with EOC in family of Ashkenazi jewish descent
• Two 1st or 2nd degree relatives with EOC on same side of family especially if:
• additional relative with breast or ovarian cancer
• age <40 y at diagnosis
• ## bilateral breast cancer

Question 3

What percentage of endometrial cancer can be attributed to a hereditary cancer syndrome?

Answer 3

5%

Question 4

What percentage of epithelial ovarian cancers can be attributed to a familial cancer syndrome

Answer 4

20%

Question 5

Name the relevant familial genetic syndromes

Answer 5

Hereditary breast and ovarian cancer (BRCA1 and 2)
Lynch syndrome (HNPCC)
Cowden - rare
Peutz-jeghers - rare
Li-Fraumeni - rare

Question 6

Which histological subtypes of ovarian cancer are more of a red flag for an underlying familial syndrome?

Answer 6

high grade serous and endometrioid cancers

vs less aggressive cancers such as mucinous

Question 7

what is the threshold for offering combined BRCA1 and 2 gene testing?

Answer 7

A combined BRCA1 and 2 mutation carrier probability of 10% or more

Question 8

What percentage reduction in risk of ovarian cancer is gained by risk reducing surgery in the setting of BRCA1/2 mutations?

Answer 8

80-96% risk reduction

Question 9

At what age does a woman with BRCA1 mutation have an increase in risk of ovarian cancer?

Answer 9

in her 40s

Question 9

At what age does a woman with BRCA1 mutation have an increase in risk of ovarian cancer?

Answer 9

in her 40s

Question 10

At what age does a woman with BRCA2 mutation have an increase in risk of ovarian cancer?

Answer 10

> 45 y

Question 11

What is STIC?

Answer 11

serous tubal intra-epithelial carcinoma

- the lesion that is associated with many BRCA mutation ovarian cancers

Question 12

Is there a place for a screening program for ovarian cancer?

Answer 12

• not enough evidence to use ca125 and USS yest

UKFOCCs study awaited

Question 13

what are PARP inhibitors?

Answer 13

poly (ADP-ribose) polymerase (PARP) inhibitors

PARP inhibitors lead to mutated cells’ death

Question 14

What IS BRCA 1 and 2?

Answer 14

BRCA is a human tumour supressor gene
BRCA mutations are mutations in these tumour suppressor genes
When mutations occur, and are not suppressed, malignancy occurs

Question 15

What is LYNCH syndrome caused by?

Answer 15

a germline mutation in the DNA mismatch repair genes

results in increased risk of multiple types of canceers

Question 16

Which cancers are associated with LYNCH syndrome?

Answer 16

colorectal
endometrial
ovarian
gastric
small bowel
hepatobiliary
brain
ureteric
renal
pelvic

Question 17

What is the risk of endometrial cancer in a woman with LYNCH syndrome cf general population?

Answer 17

Lifetime risk of 40-60% vs 3%

Question 18

What is the risk of ovarian cancer in a woman with LYNCH syndrome cf general population?

Answer 18

10-12% cf 1.4% general population

Question 19

What is the Amsterdam criteria?

Answer 19

series of clinical criteria that are used to identify families at risk of LYNCh syndrome:

• 3 or more relatives with associated cacner
• 2 or more successive generations affected
• 1 or more relative diagnosed before the age of 50
• 1 should be a 1st degree relative of the other two
• FAP should be excluded in the case of colorectal cacner
• tumours should be verified by pathological examination

Question 20

What is the risk reducing surgery offered for women with LYNCH syndrome?

Answer 20

• TAH BSO

Question 21

What other options if risk reducing surgery is not tolerable for a woman could =you consider in context of LYNCH syndrome?

Answer 21

low dose aspirin - unclear

Question 22

What is Cowden syndrome?

Answer 22

Describes germline mutation in the tumour suppressor gene PTEN
associated with a lifetime risk in women of endometrial cancer of around 30%

Question 23

What is Peutz-jegher syndrome?

Answer 23

germline mutation of STK11 gene
associated with increased risk of gynaecological malignancy
also present with pigmented lesions on buccal mucosa and lipsWh

Question 24

What is Li-Fraumeni syndrome?

Answer 24

Germline TP53 mutation

- young onset sarcomas, breast cancer, adrenocortical tumour and childhood tumours