Genetics Flashcards

1
Q

What chromosome is BRCA1 on?

A

17q

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2
Q

What chromosome is BRCA2 on?

A

13q

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3
Q

What are BRCA1 and 2

A

Tumour suppressor genes

Play a role in DNA repair

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4
Q

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

A

85%

RCOG SIP

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5
Q

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

  • BRCA1 mutation
  • BRCA2 mutation
A
  • 63%
  • 27%

RCOG SIP

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6
Q

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

A

35-40 years

Risk increases significantly during her 40s

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7
Q

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

A

May be delayed until age 45

Risk increases later than with BRCA1

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8
Q

What ovarian tumours are associated with BRCA1 and BRCA2 mutations?

A

Epithelial tumours

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

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9
Q

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

A

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

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10
Q

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

A
  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
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11
Q

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

A
  1. 1-6% risk primary peritoneal cancer
  2. Surgical menopause
    - cardiovascular, bone, psychosexual health. Offer HRT (unless personal hx breast cancer)
  3. Surgical risks
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12
Q

What is Lynch syndrome caused by?

A

Germ line mutations in the DNA mismatch repair genes

MSH2, MLH1, MSH6, PMS2

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13
Q

How is Lynch Syndrome inhereted?

A

Autosomal dominant

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14
Q

What cancers is Lynch Syndrome associated with?

A

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

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15
Q

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

A

40-60%
(c.f 3%)

RCOG SIP

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16
Q

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

A

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

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

RCOG SIP

17
Q

What is Cowden Syndrome?

A

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

18
Q

What is Peutz-Jegher’s Syndrome?

A

Germ line mutation in the STK11 gene
Autosomal dominant

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

19
Q

What is Li-Fraumeni syndrome?

A

Germ line mutation of TP52

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

20
Q

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

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

2018