Genetic Predisposition to cancer COPY COPY

Question 1

Where do somatic mutations occur

Answer 1

In non-germline tissues so are non-heritable

Question 2

Where are germline mutations found

Answer 2

In eggs or sperm so they are heritable and can cause cancer family syndromes

Question 3

Which genetic processes are associated with cancer

Answer 3

Oncogenes
Tumour suppressor genes
DNA damage-response genes

Question 4

What are tumours considered to be

Answer 4

Clonal expansions

Question 5

What are proto-oncogenes

Answer 5

A normal gene that codes for proteins to regulate cell growth and differentiation

Question 6

What can cause a proto-oncogene to become an oncogene

Answer 6

Mutations

Question 7

What does one mutation in an oncogene do

Answer 7

Accelerate cell division

Question 8

What are tumour suppressor genes

Answer 8

The cell’s brakes for cell growth

Question 9

What are benign tumours

Answer 9

Tumours which are unable to metastasise

They rarely or never become cancerous but can still cause negative health effects due to pressure on other organs

Question 10

What are the risk factors for breast cancer

Answer 10

Nulliparity
Estrogen use
Dietary factors (e.g. alcohol)
Lack of exercise
Ageing
Family history
Early menarche
Late menopause

Question 11

Which genes can cause hereditary cancer

Answer 11

BRCA1
BRCA2
TP53
PTEN

Question 12

What are the risk factors of colorectal cancer

Answer 12

Ageing
Personal history of CRC or adenomas
High-fat, low-fibre diet
Inflammatory bowel disease
Family history of CRC

Question 13

What are adenomas seen as in colorectal cancer

Answer 13

Dysplastic

Question 14

Which genes are associated with cancer

Answer 14

Oncogenes
Tumour suppressor genes
DNA damage-response genes

Question 15

How many mutations are required in an oncogene for cancer development

Answer 15

1

Question 16

How do tumour supressor genes act as a cell’s brakes

Answer 16

They inhibt the cell cycle or promote apoptosis or both

Question 17

When does cancer arise in regards to tumour supressor genes

Answer 17

When BOTH breaks fail

Question 18

How many mutations are required in tumour supressor genes for cancer development

Answer 18

2

Question 19

What are DNA damage response genes

Answer 19

The repair mechanics for DNA

Question 20

How many mutations are required in DNA damage response genes for cancer development

Answer 20

2

Question 21

What happens when both genes fail in DNA damage response genes

Answer 21

It speeds the accumulation of mutations in other critical genes

Question 22

What is HNPCC

Answer 22

Hereditary nonpolyposis colorectal cancer

Question 23

How does HNPCC arise

Answer 23

From the failure of mismatch repair (MMR) genes

So a base pair mismatch will not undergo DNA repair causing another base to be inserted (so 2 wrong bases present)

Question 24

What does mismatch repair failure lead to

Answer 24

Microsatellite instability (MSI)

Question 25

What occurs in microsatellite instability (MSI)

Answer 25

Novel Microsatellite fragments (simple sequence repeats - SSRs) are created

Question 26

What do mismatch repair (MMR) genes do

Answer 26

Correct errors that spontaneously occur during DNA replication like single base mismatches or short insertions and deletions

Question 27

What is phenotypic evidence that MMR is not functioning normally

Answer 27

The presence of MSI

Question 28

What are dysplastic cells

Answer 28

Cells that show abnormalities of appearance & cell maturation The are benign but could progress to malignancy so are known as pre-malignat

Question 29

What are malignant tumours

Answer 29

Tumours which can metastasise

Question 30

Give an example of an oncogene

Answer 30

RET

Question 31

Give an example of a cancer syndrome an oncogene can cause

Answer 31

MEN2 (Multiple endocrine neoplasia) | Familial medullary thyroid cancer

Question 32

Give an example of a tumour suppressor gene

Answer 32

BRCA1, BRCA2 APC P53 RB

Question 33

Give an example of a cancer syndrome a tumour suppressor gene can cause

Answer 33

Breast/ovarian cancer Li-Fraumeni syndrome Retinoblastoma

Question 34

Give an example of a DNA repair gene

Answer 34

MLH1, MSH2, MSH6, PMS1, PMS2

Question 35

Give an example of a cancer syndrome a DNA repair gene can cause

Answer 35

HNPCC | Lynch Syndrome

Question 36

What are the other causes of cancer

Answer 36

Autosomal recessive syndromes (e.g. MYH polyposis)

Question 37

Where do de novo mutations occur

Answer 37

In the germ cell of a parent that has no family history of hereditary cancer syndrome

Question 38

Where are de novo mutations common

Answer 38

Familial adenomatous polyposis Multiple endocrine neoplasia 2B Hereditary retinoblastoma

Question 39

Why do most cancer susceptibility genes , which are dominant show incomplete penetrance

Answer 39

The individuals inherit altered cancer susceptibility gene not cancer

Question 40

What is retinoblastoma

Answer 40

The most common eye tumor in children that can occur in heritable and nonheritable forms Identifying at-risk infants substantially reduces morbidity and mortality

Question 41

Describe the features of inherited retinoblastoma

Answer 41

Tumour: Usually bilateral Average age at diagnosis: Under Increased risk of second primaries: Osteosarcoma, other sarcomas, melanoma, others

Question 42

How many mutations are required for colorectal cancer to occur

Answer 42

Multiple

Question 43

How many adenomas occur in non-polyposis hereditary CRC syndromes

Answer 43

few to none

Question 44

How many adenomas occur in polyposis hereditary CRC syndromes

Answer 44

Multiple

Question 45

Give examples of polyposis hereditary CRC syndromes

Answer 45

FAP – severe colonic polyposis +/- CRC AFAP - less severe colonic polyposis +/-CRC MAP – varying degrees of colonic polyposis +/- CRC

Question 46

What is FAP, AFAP and MAP

Answer 46

FAP – familial adenomatous polyposis AFAP – attenuated FAP MAP – MYH associated polyposis

Question 47

What are the clinical features of HNPCC

Answer 47

Early but variable age at CRC diagnosis ( about 45 years) Tumor site throughout colon rather than descending colon Extracolonic cancers: ovary, stomach, urinary tract

Question 48

What are the clinical features of FAP

Answer 48

Risk of extracolonic tumors (upper GI, desmoid, osteoma, thyroid, brain, other) CHRPE may be present

Question 49

What are the clinical features of FAP

Answer 49

Risk of extracolonic tumors (upper GI, desmoid, osteoma, thyroid, brain, other) CHRPE (Congenital Hypertrophy of the Retinal Pigment Epithelium) may be present

Question 50

What are the clinical features of attenuated FAP

Answer 50

``` Later onset (CRC about age 50) Few colonic adenomas Not associated with CHRPE Upper GI lesions Associated with mutations at 5' and 3' ends of APC gene ```

Question 51

What are the clinical features of attenuated FAP

Answer 51

``` Later onset (CRC about age 50) Few colonic adenomas Not associated with CHRPE Upper GI lesions Associated with mutations at 5' and 3' ends of APC gene ```

Question 52

What are the meatures of MYH polyposis

Answer 52

Upper GI lesions (similar to attenuated FAP) Common mutations in mut- MYH gene Recessive inheritance

Question 53

How is cancer managed in adenomatous polyposis syndromes

Answer 53

Through: Surveillance Surgery Chemoprevention

Question 54

Polymorphisms, mutations and variants of unknown significance may

Answer 54

Have no difference or have a huge difference

Question 55

What advances in technology are helping in cancer studies

Answer 55

Exome sequencing - looks for misprints in exons | Genome sequencing - looks for misprints in the whole genome

Question 56

What do inherited mutations cause

Answer 56

An increased predisposition to cancer | Only a small proportion of cancers are due to inherited mutations