Intro to clinical cancer genetics

Question 1

What does Array-CGH pick up?

Answer 1

Pick up smaller changes in DNA

Question 2

What does genetic variation make up?

Answer 2

Makes us unique

Question 3

What is genetic variation the basis for?

Answer 3

• Basis for evolution

- Basis for disease

Question 4

What is genetic variation caused by?

Answer 4

• Caused by intrinsic errors in DNA replication and repair

- Caused by external factors

Question 5

What does cancer result from?

Answer 5

Cancer results when mutations accumulate, cell does not die and cell growth is uncontrolled

Question 6

What are most cancers caused by?

Answer 6

Most cancers are caused by a combination of genetic, environmental and lifestyle factors – multifactorial/sporadic

Question 7

Germline mutations

Answer 7

• Present in egg or sperm
• Can be inherited
• Cause cancer family syndrome

Question 8

Somatic mutations

Answer 8

• Occur in nongermline tissue

- Cannot be inherited

Question 9

Sporadic cancer

Answer 9

• No increased risk of other cancers
• Usually small increased risked to relatives
• No genetic testing indicated
• Normal clinical management for affected individuals

Question 10

Hereditary cancer

Answer 10

• High risk of recurrence
• High cancer risk in relatives
• Can offer testing to individuals at risk
• Offer screening and preventative management to gene carriers

Question 11

What was knudsons 2 hit hypothesis developed for?

Answer 11

Developed for retinoblastoma

Question 12

What does knudsons 2 hit hypothesis show?

Answer 12

Shows why hereditary cancers occur at young ages and tend to be multiple

Question 13

What does Rb1 gene cause and how many faulty copies are needed?

Answer 13

Rb1 gene mutation caused retinoblastoma

-Need two faulty copies of the gene for this to occur

Question 14

What is reduced penetrance?

Answer 14

NOT every person with a germline mutation develops the disease

Question 15

What classes are targeted in cancer?

Answer 15

Different classes of genes are targeted in cancer, which function in normal cell regulation

• Growth promoting proto-oncogenes
• Growth inhibiting tumour suppressor genes
• Genes involved in DNA damage repair

Question 16

How many family generation do we take in clinical cancer genetics?

Answer 16

3 generation family history

Question 17

What do we ask when taking family history in clinical cancer genetics?

Answer 17

• Ask about consanguinity
• Ethnic background
• Types and ages of all cancers in family

Question 18

Why may we get someone with no family history of cancer?

Answer 18

• May be because of reduced penetrance
• May be because of small family
• May not know all details about their family

Question 19

What are the implication for individuals in cancer?

Answer 19

• Recurrence risks

- Risks of other cancers

Question 20

What are the implication for relatives on cancer?

Answer 20

• How to share information
• Concerns about children
• Predictive testing

Question 21

What are the insurance implications of cancer?

Answer 21

Current moratorium for predictive testing

Question 22

What are BRCA1 and BRCA2 genes functionr?

Answer 22

Function in repair of double stranded DNA breaks

Question 23

What are BRCA1 and BRCA2 genes responsible for?

Answer 23

~ 16% familial breast cancers
~ 5% breast cancer
~ 10% ovarian cancer

Question 24

What screening do we use for BRCA carriers?

Answer 24

Breast screening

Question 25

When do we carry out breast screening and what type of scans?

Answer 25

30-50 yr annual MRI screening - MRI done as breast tissue in younger women is dense so MRI helps diagnosis - 30-50 yr annual mammograms

Question 26

What does surgical options for breast cancer reduce?

Answer 26

Risk reducing double mastectomy

Question 27

What does surgical options for ovarian cancer reduce and what is removed?

Answer 27

Risk reducing bilateral salpingo-oophorectomy - Both ovaries and tubes removed - surgical menopause - Means that no longer will have oestrogen which is a protector against cardiovascular problems

Question 28

What is hereditary non-polyposis colorectal cancer syndrome also known as?

Answer 28

Lynch syndrome

Question 29

What mutations cause lynch syndrome?

Answer 29

Germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2)

Question 30

What does lynch syndrome have a hereditary predisposition to?

Answer 30

- Colorectal cancer - Ovarian cancer - Endometrial cancer - Plus gastric, pancreatic, hepatobiliary tract, urothelial and small intestine cancers

Question 31

How do we screen for HNPCC and when do we do it?

Answer 31

Colonoscopy every 18-24 months, from age 25-30

Question 32

What is recommended for HNPCC?

Answer 32

Recommend total hysterectomy

Question 33

What options are discussed for HNPCC?

Answer 33

Discuss option of risk-reducing TAH/BSO from early 40’s

Question 34

How do we test for lynch syndrome?

Answer 34

- Tumour testing on colorectal and endometrial cancers | - Gene panel testing for MLH1/MSH2/MSH6/PMS2

Question 35

What does aspirin reduce?

Answer 35

Aspirin reduces cancer risk in Lynch syndrome patients by ~50%