Genetics

Question 1

What chromosome is BRCA1 on?

Answer 1

17q

Question 2

What chromosome is BRCA2 on?

Answer 2

13q

Question 3

What are BRCA1 and 2

Answer 3

Tumour suppressor genes

Play a role in DNA repair

Question 4

WhWhat is the lifetime risk of breast cancer (by age 70) for women with BRCA1 and BRCA2 mutations?

Answer 4

85%

RCOG SIP

Question 5

What is the lifetime risk of ovarian cancer (by age 70) in women with

• BRCA1 mutation
• BRCA2 mutation

Answer 5

• 63%
• 27%

RCOG SIP

Question 6

For women with BRCA1 mutation, at what age is RRBSO recommended?

Answer 6

35-40 years

Risk increases significantly during her 40s

Question 7

For women with BRCA2 mutation, at what age is RRBSO recommended?

Answer 7

May be delayed until age 45

Risk increases later than with BRCA1

Question 8

What ovarian tumours are associated with BRCA1 and BRCA2 mutations?

Answer 8

Epithelial tumours

High-grade serous
Endometrioid carcinomas
Typically aggressive and present at an advanced stage

Question 9

What medical therapy may be beneficial in women with BRCA1/2 mutations?

Answer 9

COCP
Use associated with 50% reduction in risk of ovarian cancer

BUT COCP is UKMEC 3 in women with BRCA1/2 mutation because of risk of breast cancer. So probs would not recommend it

Question 10

What are three advantages of RRBSO in women with BRCA mutations?

Answer 10

1. 80-96% decrease in ovarian cancer risk
2. Decreases breast cancer risk by approximately half (RR greatest if surgery performed < 40)
3. Prolongs survival, 60-76% reduction in overall mortality

Question 11

What are three disadvantages of RRBSO in women with BRCA mutations?

Answer 11

1. 1-6% risk primary peritoneal cancer
2. Surgical menopause
   - cardiovascular, bone, psychosexual health. Offer HRT (unless personal hx breast cancer)
3. Surgical risks

Question 12

What is Lynch syndrome caused by?

Answer 12

Germ line mutations in the DNA mismatch repair genes

MSH2, MLH1, MSH6, PMS2

Question 13

How is Lynch Syndrome inhereted?

Answer 13

Autosomal dominant

Question 14

What cancers is Lynch Syndrome associated with?

Answer 14

Endometrial, ovarian
Colorectal, gastric, small bowel, hepatobiliary
Ureteric and renal pelvis
Brain

Question 15

What is the lifetime risk of endometrial cancer in women with Lynch Syndrome?

Answer 15

40-60%
(c.f 3%)

RCOG SIP

Question 16

What is the lifetime risk of ovarian cancer in women with Lynch Syndrome?

Answer 16

10-12%
(c.f. 1.2%)

Usually early stage and moderately or well differentiated (unlike BRCA)

RCOG SIP

Question 17

What is Cowden Syndrome?

Answer 17

Germ line mutation in the tumour suppressor gene PTEN
Autosomal dominant

PTEN harmatoma tumour syndrome
Cancer predisposition syndrome characterised by
- lifetime risk of endometrial cancer approx 30%
- increased risk of several tumour types: breast, thyroid, endometrial, colorectal, melanoma, renal cell carcinoma
- macrocephaly
- multiple hamartomas

Sparse data regarding risk-reducing total hysterectomy but may be offered

Question 18

What is Peutz-Jegher’s Syndrome?

Answer 18

Germ line mutation in the STK11 gene
Autosomal dominant

Increased risk of breast, GI and gynaecological tumours
Gastrointestinal polyposis disorder. Characterised by melanin spots

Question 19

What is Li-Fraumeni syndrome?

Answer 19

Germ line mutation of TP52

Young onset sarcomas, breast cancer, adrenocortical carcinoma, childhood tumours

Question 20

What was the finding of the Cochrane review looking at RRBSO in BRCA1/2

Answer 20

RRBSO may
- increase overall SURVIAL
- lower HGSC rates and mortality 
- lower breast cancer rates and mortality
For BRCA 1 and 2 carriers

2018