Genetic Predisposition to Cancer

Question 1

What are somatic mutations?

Answer 1

Most common form of cancer where cells iwhtin the body, not the germline, develop genetic alterations.

Question 2

Where do somatic mutations occur?

Answer 2

Occur in nongermline tissues

Question 3

Are somatic mutations inheritable?

Answer 3

No

Question 4

Where do germline mutations arise from?

Answer 4

Present in egg or sperm

Question 5

Are germline mutations inheritable?

Answer 5

Yes and can cause family cancer syndromes.

Question 6

Describe what is meant by the fact that tumours are clonal expressions.

Answer 6

-A normal cell develops an alteration and then through the daughter cells copying and dividing, more mutations can be acquired.
As more critical mutations arise, you may get a tumour with the potential to metastasise.

Question 7

Wat are proto-oncogenes?

Answer 7

Normal gene that codes for proteins to regulate cell growth and differentiation.

Question 8

What changes a proto-oncogene into an oncogene?

Answer 8

Mutations

Question 9

What can oncogenes do to cell division?

Answer 9

Accelerates the process

Question 10

How many mutations is sufficient enough for the fomration of cancer?

Answer 10

1

Question 11

What are Tumour suppressor genes?

Answer 11

The cell’s brakes for cell growth as genes can inhibit the cycle, promote apoptosis or both.

Question 12

When does cancer occur?

Answer 12

If both Tumour suppressor genes do not function and not not ‘brake’.

Question 13

How many hits on Tumour suppressor genes does it take for cancer to arise?

Answer 13

2 as two brake mechanisms

(inhibition and apotosis).

Question 14

What are DNA damage-response genes?

Answer 14

The repair mechanics for DNA

Question 15

When does cancer arise relating to DNA damage-response genes?

Answer 15

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

Question 16

What does mismatch repair do?

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Answer 16

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

Question 17

What are microsatellites?

Answer 17

Microsatellites (aka Simple Sequence Repeats SSR) are repeated sequences of DNA, can be made of repeating units of 1 – 6 base pairs

Question 18

What is MSI?

(Microsatellite instability)

Answer 18

MSI (changes in microsatellite sequences) is the phenotypic evidence that MMR is not functioning normally – genetic hypermutability

Question 19

Describe benign tumours.

Answer 19

-Lacks ability to metastasize.
-Rarely or never become cancerous.
-Can still cause negative health effects due to pressure on other organs.

Question 20

Define malignant tumours.

Answer 20

Able to metastasize.

Question 21

Describe dysplastic tumours.

Answer 21

Benign but could progress to malignancy. Cells show abnormalities of appearance & cell maturation. Sometimes referred to as ‘pre-malignant’.

Question 22

Give examples of some Dominantly Inherited Cancer Syndromes and then gene process and genes that cause them.

Answer 22

Familial medullary thyroid cancer- RET genes in oncogenes
Breast/ovarian cancer- BRCA1, BRCA2 in tumour suppressor genes
HNPCC / Lynch Syndrome- MLH1, MSH2, MSH6, PMS1, PMS2 in DNA repair/ DNA mismatch repair

Question 23

What are de novo mutations?

Answer 23

New mutation in an individual present in the germline but not in their parents

Question 24

What is retinoblastoma?

Answer 24

Most common eye tumour in children

Question 25

List some of the risk factors of breast cancer.

Answer 25

Ageing
Family history
Early menarche
Late menopause
Nulliparity
Estrogen use
Dietary factors (eg: alcohol)
Lack of exercise

Question 26

List some of the high risk genes contributing to familial breast cancer.

Answer 26

BRCA1
BRCA2

Question 27

List some of the moderate risk genes contributing to familial breast cancer.

Answer 27

CHEK2 heterozygous mutation
BRIP1

Question 28

List some of the high risk genes contributing to familial ovarian cancer.

Answer 28

BRCA1
BRCA2

Question 29

List some of the moderate risk genes contributing to familial ovarian cancer.

Answer 29

PALB2
BARD1

Question 30

List some risk factors for Colorectal Cancer (CRC)

Answer 30

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

Question 31

List some clinical features of HNPCC

Answer 31

-Early but variable age at CRC diagnosis (~45 years)
-Tumour site throughout colon rather than descending colon

Question 32

List some clinical features of HNPCC

Answer 32

-Early but variable age at CRC diagnosis (~45 years)
-Tumour site throughout colon rather than descending colon

Question 33

Give a few examples pf extracolonic cancers

Answer 33

Extracolonic cancers: endometrium, ovary, stomach, urinary tract, small bowel, bile ducts, sebaceous skin tumors

Question 34

What does Non-polyposis mean?

Answer 34

Few to no adenomas

Question 35

What does polyposis mean?

Answer 35

Several adenomas.

Question 36

List some clinical features of FAP (familial adenomatous polyposis)

Answer 36

Estimated penetrance for adenomas >90%
Risk of extracolonic tumors (upper GI, desmoid, osteoma, thyroid, brain, other)
CHRPE (Congenital hypertrophy of the retinal pigment epithelium) may be present
Untreated polyposis leads to 100% risk of cancer

Question 37

Describe Attenuated FAP

Answer 37

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

Question 38

How is cancer risk in Adenomatous Polyposis syndromes managed?

Answer 38

Surveillance
Surgery
Chemoprevention

Question 39

Those with family history of cancer…

Answer 39

are more likely to get it

Question 40

Who does genetic counselling?

Answer 40

Clinical geneticist
Genetic counsellor
Hospital doctor
GP
Nurse…

->GP’s and nurses more as beginning to mainstream genetic testing so some is undertaken by these professionals.