Genetics

Question 1

What are some of the causes of hereditary susceptibility to colorectal cancer ?

Answer 1

Sporadic (65%)
Rare CRC Syndromes
Lynch syndrome
Familial

Question 2

What are the 2 types of mutations which occur and can predispose people to cancer ?

Answer 2

Germaline mutations

Somatic mutations

Question 3

Which type of mutations cause cancer family syndromes ?

Answer 3

Germaline Mutations

Question 4

Which type of gene mutations are nonheritable ?

Answer 4

Somatic mutations

Question 5

Where in the cell cycle do oncogenes contribute ?

Answer 5

After G1 (Cell growth)

Question 6

Where in the cell cycle do tumor suppressor genes contribute ?

Answer 6

Between G0 and Synthesis (S)

Question 7

Where in the cell cycle does DNA repair genes ?

Answer 7

Between synthesis and G2

Question 8

How many mutations are need for cancer development ?

Answer 8

1 Mutation is sufficient for role in cancer development ?

Question 9

In cancer what takes a normal epithelium to a hyper-proliferative epithelium ?

Answer 9

Loss of APC

Question 10

In cancer what takes an early adenoma to an intermediate adenoma ?

Answer 10

Activation of K-ras

Question 11

In cancer what takes an intermediate adenoma to a late adenoma ?

Answer 11

Loss of 18q

Question 12

In cancer what takes a late adenoma to a carcinoma ?

Answer 12

Loss of TP53

Question 13

What is the main mechanism for familial cancer ?

Answer 13

Faulty DNA mismatch repair

Question 14

What is Lynch syndrome/Hereditary Non-Polyposis Colon Cancer ?

Answer 14

Mutation in mismatch repair genes

Excess of colorectal, endometrial, urinary tract, ovarian and gastric cancers.

Question 15

What are the clinical features of Hereditary Non-Polyposis Colon Cancer ?

Answer 15

Early but variable age

Tumour site in proximal colon predominates

Question 16

What areas in the body are cancer most likely in Lynch syndrome ?

Answer 16

Colon

Endometrial

Question 17

What does autosomal dominant inheritance mean ?

Answer 17

Each child has 50% chance of inheriting the mutation

No skipped generations

Equally transmitted by men and women

Question 18

When should you suspect hereditary cancer syndrome ?

Answer 18

Cancer in 2 or more close relatives

Early age at diagnosis

Multiple primary tumors

Bilateral or multiple rare cancers

Question 19

What is the surveillance for colorectal cancer ?

Answer 19

Colonoscopy

Question 20

If you are a gene carrier for CRC how often should you surveyed ?

Answer 20

2x yearly from 25/35

Question 21

If you are moderate risk for CRC how often should you be surveyed ?

Answer 21

5 yearly from 50

Question 22

What are the benefits of genetic testing ?

Answer 22

Identifies highest risk.
Identifies non-carriers in families with a known mutation.
Allows early detection and prevention strategies.
May relieve anxiety.

Question 23

What are the risks and limitations of genetic testing ?

Answer 23

Does not detect all mutations.
Continued risk of sporadic cancer.
Efficacy of interventions possible.
May result in psychological or economic harm

Question 24

Name forms of chromosomal defects

Answer 24

Numerical i.e. Trisomy 21

Structural i.e. Translocations, deletions and microdeletions

Question 25

Name forms of single gene disorders

Answer 25

Autosomal dominant i.e. Myotonic Dystrophy. Autosomal recessive i.e. CF. X-linked i.e. Duchenne muscular dystrophy

Question 26

What are the features of Neurofibromatosis Type 1 (NF1) ?

Answer 26

Autosomal dominant ``` Macroencephaly Short stature Dysmorphic features Learning difficulties Epilepsy Scoliosis Hypertensive (Renal artery stenosis) ```

Question 27

What criteria is used to diagnose NF1 ?

Answer 27

NIH criteria (need 2+ for diagnosis)

Question 28

What gene has been identified in NF1 ?

Answer 28

17q

Question 29

What are the main features of NF2 ?

Answer 29

Acoustic neuromas | CNS and spinal tumors

Question 30

Where is the NF2 gene ?

Answer 30

On chromosome 22

Question 31

What is the classical triad found in those with Tuberous Sclerosis ?

Answer 31

Epilepsy Learning difficulties Skin lesions

Question 32

What are the features of Myotonic Dystrophy ?

Answer 32

Autosomal dominant Bilateral late-onset cataract Muscle weakness, stiffness and myotonia. Diabetes. Heart block.

Question 33

What are the clinical features of ALS?

Answer 33

Progressive muscle weakness, wasting and increased reflexes. Limb and bulbar muscles involved. Pure motor signs (fasiculations) Cognition speed. Death due to resp. failure

Question 34

In humans, three forms of superoxide dismutase are present, where is SOD1 located ?

Answer 34

Cytoplasm

Question 35

Where in humans is SOD2 located ?

Answer 35

Mitochondria

Question 36

Where in humans is SOD3 located ?

Answer 36

Extracellular

Question 37

Where are the genes fro SOD 1, 2 and 3 located ?

Answer 37

Chromosomes 21, 6 and 4

Question 38

What does the presence of SOD do for the body ?

Answer 38

Protects many types of cell from free radical damage that is important in ageing and ischaemic tissue damage.

Question 39

What is the unique mutation identified in huntington's disease ?

Answer 39

CAG expansion

Question 40

What are the clinical features of huntingtons ?

Answer 40

``` Movement disorder Chorea Athetosis Myoclonus Rgidity ``` Onset early 30s/40s