Genetic predisposition of cancer

Question 1

what type of mutation causes a missing/non-working protein?

Answer 1

Truncating mutation.

Question 2

How do most mutations cause disease?

Answer 2

Through haploinsufficiency.

(when 1 copy is not working and the other copy can’t do the job on its own).

Question 3

how much of ovarian cancer is hereditary?

Answer 3

5-10%

Question 4

how much of breast cancer is hereditary?

Answer 4

5-10%

Question 5

what is the main mutation causing hereditary ovarian cancer?

Answer 5

BRCA1

BRCA2

Question 6

what is a somatic mutation?

Answer 6

A mutation which occurs in one cell and can’t be inherited.

only tissues which have derived from the mutated cell are affected

Question 7

What is a germ-line mutation?

Answer 7

Occurs in gametes and will be passed on, every cell will be affected by the mutation.

Question 8

how much of colorectal cancer is hereditary?

Answer 8

10-30%

Question 9

how much of colorectal cancer is caused by Lynch syndrome?

Answer 9

5%

Question 10

how much colorectal cancer is caused by familial adenomatous polyposis.

Answer 10

1%

Question 11

what type of mutation is the cause of most cancers?

Answer 11

Somatic mutation.

Question 12

Where are proto-oncogenes and tumour suppressor genes within the cell cycle?

Answer 12

1st half = proto-oncogenes.

2nd half = tumour suppressor genes.

Question 13

what is the role of proto-oncogenes?

Answer 13

they encourage cell growth.

Question 14

what is the role of tumour suppressor genes?

Answer 14

they cause cell repairs and tell a cell when to do apoptosis.

Question 15

which type of mutation is oncogenes more common in?

Answer 15

sporadic (non familial)

Question 16

what type of mutation is tumour suppressor genes more common in?

Answer 16

germ-line (familial).

Question 17

which oncogene is associated with leukaemia?

Answer 17

oncogene ABL.

Question 18

what is retinoblastoma?

Answer 18

uncontrolled growth of the cells in the retina.

Question 19

what is the main sign of retinoblastoma?

Answer 19

leukocorea - white pupil in flash picture instead of red.

Question 20

what causes retinoblastoma?

Answer 20

It can be familial or sporadic.

Question 21

what is carcinogenesis?

Answer 21

this is a long multistep process that transforms normal cells into cancerous ones.

Question 22

in which type of cancer is the multi-step carcinogenesis obvious?

Answer 22

In colon cancer.

Normal epithelium - hyper proliferation - adenoma - carcinoma - metastasis.

Question 23

what is the benefit of having clear cut stages of carcinogenesis?

Answer 23

For example in colon cancer - you can intervene at the adenoma stage.

Question 24

which cancers do not have clear carcinogenesis stages?

Answer 24

Breast cancer

ovarian cancer

Question 25

what is the most common mechanism for familial cancer?

Answer 25

when an extra base is added and is not removed like it usually should be.

Question 26

what is Lynch syndrome/ hereditary non polyposis colorectal cancer?

Answer 26

caused by a mutation in mismatch repair genes (MSH1, MSH2). causes - colorectal, ovarian and endometrial cancer. Autosomal dominant

Question 27

what is the risk of colorectal or endometrial cancer in patients with Lynch syndrome?

Answer 27

``` Colorectal = 80% by the time they are 30yrs. Endometrial = 40-60% ```

Question 28

what age and where do tumours present in Lynch syndrome colorectal cancer?

Answer 28

Proximal colon | early diagnosis of CRC (45yrs)

Question 29

Which cancer is most commonly associated with BRCA1/2?

Answer 29

Breast cancer | Ovarian cancer

Question 30

What are the chances of breast or ovarian cancer with BRCA1?

Answer 30

``` Breast = 60-80% (50% get another primary breast cancer after) Ovarian = 50% ```

Question 31

What are the chances of breast and ovarian cancer with BRCA2?

Answer 31

``` Breast = 60% Ovarian = 20% ``` ALSO associated with prostate and breast cancer in Males!! (not in BRCA1)

Question 32

what is the chance of a child inheriting a gene if it is autosomal dominant?

Answer 32

50%

Question 33

what is the chance of a grandchild carrying the gene if it is autosomal dominant?

Answer 33

25%

Question 34

what are common signs of hereditary cancer syndrome?

Answer 34

cancer in 2 or more relatives early age diagnosis multiple primary tumours in the same person characteristic pattern (breast +ovary), (colorectal, endometrium and stomach)

Question 35

What are the classifications for gene carriers?

Answer 35

Low - similar to normal population Medium - High -

Question 36

what is prophylaxis for cancer?

Answer 36

``` Aspirin use (Prevents colorectal cancer in Lynch syndrome) Colon removal in FAP (prophylactic colectomy) Oestrogen - prevent breast cancer, don't use menopausal for long. ```

Question 37

what are the breast cancer surveillance options?

Answer 37

- receive first screening 5 years before first breast cancer in family - moderate/high = 2yrly (35-40), yrly(40-50), then moderate just gets the normal 3yrly after 50, high go on to get 18 monthly (50-64) - Highest risk = MRI screening.

Question 38

what treatments used for metastatic cancer for BRCA1 and BRCA2?

Answer 38

PARP inhibitor

Question 39

what cancers are associated with P53?

Answer 39

colorectal, ovarian, breast, liver, lung.

Question 40

what prophylaxis is done for BRCA1/2 carriers?

Answer 40

Mastectomy. cuts chance of breast cancer down to 5% (half the national average). Oophorectomy (induces menopause so HRT must be used).

Question 41

what is the prophylaxis for colorectal cancer?

Answer 41

Gene carrier - 2yrly colonoscopy (25-35) Moderate - colonoscopy at 55yrs or 5yrly from 50-70 Prophylactic aspirin.

Question 42

what is the prophylaxis for endometrial cancer?

Answer 42

hysterectomy | symptom awareness

Question 43

what are the main symptoms of proximal colon cancer?

Answer 43

anaemia | weight loss

Question 44

what are the main symptoms of distal colon cancer?

Answer 44

constipation change in bowel habit thin, ribbon like stools