Familial cancer syndromes Flashcards
List the lifetime risk of ovarian cancer based on number of relatives with ovarian cancer
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%
In what scenario do women need testing for BRCA mutation?
- 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
What percentage of endometrial cancer can be attributed to a hereditary cancer syndrome?
5%
What percentage of epithelial ovarian cancers can be attributed to a familial cancer syndrome
20%
Name the relevant familial genetic syndromes
Hereditary breast and ovarian cancer (BRCA1 and 2) Lynch syndrome (HNPCC) Cowden - rare Peutz-jeghers - rare Li-Fraumeni - rare
Which histological subtypes of ovarian cancer are more of a red flag for an underlying familial syndrome?
high grade serous and endometrioid cancers
vs less aggressive cancers such as mucinous
what is the threshold for offering combined BRCA1 and 2 gene testing?
A combined BRCA1 and 2 mutation carrier probability of 10% or more
What percentage reduction in risk of ovarian cancer is gained by risk reducing surgery in the setting of BRCA1/2 mutations?
80-96% risk reduction
At what age does a woman with BRCA1 mutation have an increase in risk of ovarian cancer?
in her 40s
At what age does a woman with BRCA1 mutation have an increase in risk of ovarian cancer?
in her 40s
At what age does a woman with BRCA2 mutation have an increase in risk of ovarian cancer?
> 45 y
What is STIC?
serous tubal intra-epithelial carcinoma
- the lesion that is associated with many BRCA mutation ovarian cancers
Is there a place for a screening program for ovarian cancer?
- not enough evidence to use ca125 and USS yest
UKFOCCs study awaited
what are PARP inhibitors?
poly (ADP-ribose) polymerase (PARP) inhibitors
PARP inhibitors lead to mutated cells’ death
What IS BRCA 1 and 2?
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
What is LYNCH syndrome caused by?
a germline mutation in the DNA mismatch repair genes
results in increased risk of multiple types of canceers
Which cancers are associated with LYNCH syndrome?
colorectal endometrial ovarian gastric small bowel hepatobiliary brain ureteric renal pelvic
What is the risk of endometrial cancer in a woman with LYNCH syndrome cf general population?
Lifetime risk of 40-60% vs 3%
What is the risk of ovarian cancer in a woman with LYNCH syndrome cf general population?
10-12% cf 1.4% general population
What is the Amsterdam criteria?
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
What is the risk reducing surgery offered for women with LYNCH syndrome?
- TAH BSO
What other options if risk reducing surgery is not tolerable for a woman could =you consider in context of LYNCH syndrome?
low dose aspirin - unclear
What is Cowden syndrome?
Describes germline mutation in the tumour suppressor gene PTEN
associated with a lifetime risk in women of endometrial cancer of around 30%
What is Peutz-jegher syndrome?
germline mutation of STK11 gene
associated with increased risk of gynaecological malignancy
also present with pigmented lesions on buccal mucosa and lipsWh
What is Li-Fraumeni syndrome?
Germline TP53 mutation
- young onset sarcomas, breast cancer, adrenocortical tumour and childhood tumours
