Genetic predisposition to cancer

Question 1

What do most cancers arise from

Answer 1

Genetic mutations either sporadic or inherited

Question 2

What kind of cancer mutation is non inheritable

Answer 2

somatic

Question 3

What causes germ-line mutations

Answer 3

Hereditary -present in egg or sperm of parents

Question 4

What are tumours

Answer 4

clonal expansions

Question 5

What are the three genetic processes associated with cancer syndromes

Answer 5

Oncogenes
Tumour suppressor genes
DNA damage-response genes

Question 6

What are oncogenes

Answer 6

Mutated proto-oncogens that accelerate cell division

Question 7

How many mutations are needed to active oncogenes

Answer 7

1

Question 8

What is the role tumour suppressor genes

Answer 8

Inhibit cell growth
promote apoptosis
Cells breaks

Question 9

When does cancer arrive with tumour suppressor genes

Answer 9

when both tumour suppressor genes fail

Question 10

Where does the two hit in tumour suppressor genes occur resulting from carrier to cancer

Answer 10

first - germ line (carrier)

second - tumour formation

Question 11

What do DNA damage-response genes do

Answer 11

The repair mechanics for DNA

Question 12

When does cancer arrive from DNA damage-response genes

Answer 12

both genes fail, speeding the accumulation of mutations in other critical genes

Question 13

Give an example of a DNA damage response gene MMR

Answer 13

failure to mismatch due to single base mismatches or short insertions and deletions leads to accumulation of nucleotide repeats - Microsatellite instability

Question 14

What is the evidence that DNA damage response genes aren’t working

Answer 14

Microsatellite instability

Question 15

What is de novo mutations

Answer 15

mutations occurring in there germ line of parents with no family history of hereditary cancer

Question 16

How do we look for inherited cancers

Answer 16

family history

Question 17

What are most cancer susceptible genes

Answer 17

autosomal dominant with incomplete penetrance - therefore have genes but do not show the symptoms

Question 18

What is sporadic cancer

Answer 18

cancer by chance

Question 19

If tumours are heritable they are usually bilateral with increases the risk of what and why

Answer 19

secondary primer

because every cell carries the mutation

Question 20

How is Retinoblastoma cancer occur

Answer 20

due to heritable or non heritable tumour supressor genes

Question 21

What are the risks factors for breast cancer

Answer 21

Ageing 
Family history 
Hormones - late menopause/pill/HRT
Dietary factors 
Lack of exercise

Question 22

What is the most likely and second most likely gene to causes breast cancer and by what mutation

Answer 22

BRCA 1 then BRCA2

spordic

Question 23

What is BRCA1 genes functions

Answer 23

Checkpoint mediator

DNA damage signalling and repair

Chromatin remodelling (inactive Xchromosome)

Question 24

What is BRCA2s functions

Answer 24

DNA repair by HR (homologous recombination)

Question 25

What else can BRCA1/2genes cause

Answer 25

Secondary breast cancer Ovarian cancer Male breast cancer

Question 26

What cancer conditions can arise from tumour suppressor gene

Answer 26

Breast cancer ovarian cancer Retinoblastoma

Question 27

What are the risk factors for colorectal cancer

Answer 27

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

Question 28

How does Hereditary nonpolyposis colorectal cancer occur

Answer 28

DNA Mismatch Repair of HNPCC gene

Question 29

what does polyposis and non polyposis mean

Answer 29

multiple adenomas present | No adenomas - but there is a risk of development

Question 30

Lynch syndrome aka HNPCC is what

Answer 30

autosomal dominant genetic condition that has a high risk of colon cancer

Question 31

What gene causes severe polyposis in colon cancer

Answer 31

FAP - familial adenomatous polyposis

Question 32

What is clinical features of HNPCC

Answer 32

Tumor site throughout colon rather than descending colon | Extracolonic cancers: endometrium, ovary, stomach, urinary tract, small bowel, bile ducts, sebaceous skin tumors

Question 33

Clinical Features of FAP

Answer 33

Estimated penetrance for adenomas >90% Risk of extracolonic tumors Untreated polyposis leads to 100% risk of cancer

Question 34

What is autosomal recessive cancer syndrome and example

Answer 34

need to Inherit copies in both parents to show symptoms e.g. MYH polyposis

Question 35

What explains a family with history of cancer but no identified mutation

Answer 35

Multiple modifier genes of lower genetic risk

Question 36

How are cancer risk in Adenomatous Polyposis syndromes treated

Answer 36

Surveillance Surgery Chemoprevention