Molecular And Genetic Basis Of Inherited Cancer Risk In Gynaecology TOG 2015

Question 1

What % of cancers are as a result of acquired mutation(sporadic) ?

Answer 1

90% and the commonest cause of cancer

Question 2

What % of cancers are due to inherited

Answer 2

5-10%
Most are autosomal dominant

Question 3

What % of cancers are familial ?

Answer 3

10-15%
Due to multi factorial interaction between low penetrant genes and environmental factors

Question 4

Incidence of BRCA mutation in cancer patients of western populations?

Answer 4

1%

Question 5

What is the lifetime risk of breast and ovarian cancer In patients with mutation in BRCA1

Answer 5

55-65% for breast ca
59% for fallopian tube/ ovarian cancer

Question 6

What is the lifetime risk for breast and ovarian cancer in BRCA 2 mutation?

Answer 6

45% for breast cancer
11-27% for fallopian tube/ovarian cancer

Question 7

How can you distinguish Breast cancer positive BRCA1 from BRCA2

Answer 7

BRCA 1- triple negative phenotype( Er, Pr, HEr2 receptor negative)

BRCA2- Er positive but HEr2 negative.

Question 8

What is the prognosis for BRCA positive tumours

Answer 8

Good.
They are platinum based sensitive

Question 9

What % of ovarian cancers are BRCA positive

Answer 9

6.5-19%

Question 10

What’s the distinct characteristic of BRCA positive ovarian cancers

Answer 10

High grade serous histology
Advanced stage presentation
Poor differentiation
Increased incidence of visceral metastasis
High incidence of TP53 dysfunction
Improved overall survival

Question 11

What is the cumulative risk of epithelial ovarian cancer in RAD51C mutation carriers?

Answer 11

9% by the age of 80 years

Question 12

What’s the cumulative risk of EOC in RAD51D mutation carriers ?

Answer 12

10% by the age of 80 years
1:200 individuals with ovarian cancer will have the mutation

Question 13

What’s the lifetime risk of EOC in BRIP1 mutation carriers?

Answer 13

10-15-%

Question 14

What is the prevalence of HNPCC in colorectal and endometrial cancer patients ?

Answer 14

1-3%
Population incidence of 1:400 and 1:2000

Question 15

What is the most common alteration of MMR in HNPCC/Lynch syndrome

Answer 15

MLH1 and MSH2 from 90%
MSH6 10%

Question 16

What is the lifetime risk of EC in MLH1 mutation Carriers?

Answer 16

20-54%

Question 17

What is the lifetime risk of EC in MSH2 carriers?

Answer 17

21-49%

Question 18

What is the lifetime risk of EC in MSH6 mutation carriers?

Answer 18

16-17%

Question 19

What type of EC is associated with MMR gene mutation

Answer 19

Non endometroid type which is more aggressive with predeliction for lower uterine segment

Question 20

What is the prognosis of LS associated ovarian cancers ?

Answer 20

Good prognosis as diagnosed at an earlier stage compared to sporadic cases

Question 21

What is Muir Torre syndrome

Answer 21

Rare autosomal dominant syndrome characterised by Keratoacanthomas and visceral malignancy( colorectal, Urothelial and endometrial)