genetic predisposition to cancer

Question 1

what two types of gene mutations are there relating to cancer?

Answer 1

somatic and germline

Question 2

what type of mutation causes cancer family syndromes?

Answer 2

germline

Question 3

where are germline mutations present?

Answer 3

egg or sperm cells

Question 4

what is a proto-oncogene?

Answer 4

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

Question 5

what is the effect of oncogenes?

Answer 5

accelerated cell division

Question 6

what can change a proto oncogene into an oncogene?

Answer 6

mutation

Question 7

how many mutations are sufficient for oncogenes to play a role in cancer development?

Answer 7

1

Question 8

what are tumour suppressor genes?

Answer 8

cells “brakes” for cell growth

Question 9

what are the effects of tumour suppression genes?

Answer 9

inhibit cell cycle

promote apoptosis

Question 10

how many mutations must occur for tumour suppression genes to play a role in cancer development?

Answer 10

2

Question 11

what do DNA damage-response genes do?

Answer 11

repair DNA

Question 12

how many DNA damage response genes have to fail to cause cancer?

Answer 12

when both genes fail

Question 13

what does mismatch repair failure lead to?

Answer 13

microsatellite instability

Question 14

what is the effect of MMR?

Answer 14

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

Question 15

what are created as a result of defective MMR?

Answer 15

novel microsatellites fragments called simple sequence repeats

Question 16

what characterises a benign tumour?

Answer 16

tumour lacks the ability to metastasize

Question 17

what characterises a dysplastic tumour?

Answer 17

benign tumour that has the potential to progress to malignancy

Question 18

what would you see histologically in a dysplastic tumour?

Answer 18

abnormal cell appearance and cell maturation

Question 19

what characterises a malignant tumour?

Answer 19

able to metastasize

Question 20

what is a de novo mutation?

Answer 20

new mutation that occurs in germ cell of a patient

Question 21

what is a retinoblastoma?

Answer 21

most common eye tumour in children

Question 22

what is the difference between nonheritable and heritable retinoblastoma?

Answer 22

unilateral in nonheritable
usually bilateral in heritable
increased risk of second primary cancers in heritable
family history in around 20% of cases in heritable
heritable cancers typically present at a younger age

Question 23

what are some risk factors for breast cancer?

Answer 23

ageing
family history
dietary factors
lack of exercise
estrogen use

Question 24

what is the most common known gene that contributes to the development of breast cancer?

Answer 24

BRCA1

Question 25

what are some functions of BRCA1

Answer 25

checkpoint mediator DNA damage signalling and repair chromatin remodelling transcription

Question 26

what are some functions of BRCA2?

Answer 26

DNA repair by homologous recombination

Question 27

what is the risk of developing a BRCA1 associated cancer?

Answer 27

Breast - 50-85% second primary breast cancer - 40-60% ovarian cancer - 15-45%

Question 28

what is the risk of developing a BRCA2 associated cancer?

Answer 28

breast cancer: 50-85% male breast cancer: 6% ovarian cancer: 10-20%

Question 29

what are some risk factors for colorectal cancer?

Answer 29

``` ageing personal history high fat low fibre diet IBS family history of CRC ```

Question 30

what are some hereditary colorectal cancer syndromes?

Answer 30

non-polyposis | polyposis

Question 31

what is an example of a non-polyposis CRC syndrome?

Answer 31

hereditary non-polyposis colon cancer- HNPCC

Question 32

what are some example of polyposis CRC syndromes?

Answer 32

FAP - severe colonic polyposis AFAP - less severe colonic polyposis MAP - varying degrees of colonic polyposiss

Question 33

what does FAP stand for?

Answer 33

familial adenomatous polyposis

Question 34

what are some clinical features of HNPCC?

Answer 34

tumour site throughout colon rather than descending colon | can lead to the development of extracolonic cancers (endometrium, ovary)

Question 35

what are some clinical features of FAP?

Answer 35

over 90% penetrance for adenomas risk of extracolonic tumours CHRPE untreated polyposis leads to 100% risk of cancer

Question 36

what does CHRPE stand for?

Answer 36

congenital hypertrophy of the retinal pigment epithelium

Question 37

what are some clinical features of AFAP?

Answer 37

``` later onset few colonic adenomas not associated with CHRPE upper GI lesions associated with mutations at the 5' and 3' ends of APC gene ```

Question 38

what can oppose the effect of inherited cancer genes?

Answer 38

multiple modifier genes of lower gentic risk

Question 39

how are adenomatous polyposis syndromes managed?

Answer 39

surveillance surgery chemoprevention

Question 40

are the majority of cancers sporadic or inherited?

Answer 40

sporadic

Question 41

what is the effect of an inherited mutation?

Answer 41

increased PREDISPOSITION to cancer