Genetics Flashcards
What chromosome is BRCA1 on?
17q
What chromosome is BRCA2 on?
13q
What are BRCA1 and 2
Tumour suppressor genes
Play a role in DNA repair
WhWhat is the lifetime risk of breast cancer (by age 70) for women with BRCA1 and BRCA2 mutations?
85%
RCOG SIP
What is the lifetime risk of ovarian cancer (by age 70) in women with
- BRCA1 mutation
- BRCA2 mutation
- 63%
- 27%
RCOG SIP
For women with BRCA1 mutation, at what age is RRBSO recommended?
35-40 years
Risk increases significantly during her 40s
For women with BRCA2 mutation, at what age is RRBSO recommended?
May be delayed until age 45
Risk increases later than with BRCA1
What ovarian tumours are associated with BRCA1 and BRCA2 mutations?
Epithelial tumours
High-grade serous
Endometrioid carcinomas
Typically aggressive and present at an advanced stage
What medical therapy may be beneficial in women with BRCA1/2 mutations?
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
What are three advantages of RRBSO in women with BRCA mutations?
- 80-96% decrease in ovarian cancer risk
- Decreases breast cancer risk by approximately half (RR greatest if surgery performed < 40)
- Prolongs survival, 60-76% reduction in overall mortality
What are three disadvantages of RRBSO in women with BRCA mutations?
- 1-6% risk primary peritoneal cancer
- Surgical menopause
- cardiovascular, bone, psychosexual health. Offer HRT (unless personal hx breast cancer) - Surgical risks
What is Lynch syndrome caused by?
Germ line mutations in the DNA mismatch repair genes
MSH2, MLH1, MSH6, PMS2
How is Lynch Syndrome inhereted?
Autosomal dominant
What cancers is Lynch Syndrome associated with?
Endometrial, ovarian
Colorectal, gastric, small bowel, hepatobiliary
Ureteric and renal pelvis
Brain
What is the lifetime risk of endometrial cancer in women with Lynch Syndrome?
40-60%
(c.f 3%)
RCOG SIP