Familial cancer

Question 1

Causes of familial cancer

Answer 1

Genetics
Care taker genes- DNA repair, carcinogen metabolism.
Gatekeeper genes- cell cycle control

Environment
Macro- environment- chemical, viruses, radiation and physics agents.
Micro- environment- oxyradicals, hormones and growth factors.

Question 2

What is the two hit hypothesis is cancer

Answer 2

both alleles must have a mutation for the cancer to develop.

Question 3

why is it easier to develop cancer if you have I mutated gene (relate to 2 hit hypothesis)

Answer 3

In inherited cancer the first mutation is already present and therefore it is much easier to develop cancer

Question 4

define peneterance

Answer 4

percentage of people with the gene change who develop the condition.

Question 5

How does cancer develop on a cellular level

Answer 5

series of genetic changes within cells leading to abnormal behaviour and histology

Question 6

function of gatekeeper genes

Answer 6

monitor and control cell division

Question 7

function of caretaker genes

Answer 7

improve genomic stability (repair mutations

Question 8

function of landscapers

Answer 8

control the surrounding stromal environment

Question 9

what is the function of tumour suppressor genes

Answer 9

protect cells from becoming cancerous.

Question 10

what is the function of oncogenes

Answer 10

regulate cell growth and differentiation.

Question 11

examples of tumour suppressor genes

Answer 11

APC, BRAC1/2, TP53, Rb

Question 12

do tumour suppressor genes gain or lose function to become cancerous

Answer 12

loss function

Question 13

do oncogenes gain or lose function to become cancerous

Answer 13

gain function

Question 14

examples of oncogenes

Answer 14

growth and signal transduction factors , RET gene

Question 15

what is the name for the 2 hit hypothesis

Answer 15

Knudsons

Question 16

Is cancer a autosomal dominant or recessive condition

Answer 16

autosomal dominant.

Question 17

At a cellular level is cancer a dominant or recessive condition

Answer 17

recessive (2 hit hypothesis)

Question 18

Give a example of a rare autosomal recessive condition

Answer 18

MYH associated polyposis, faconi anaemia and Ataxia telaniectasia.

Question 19

What are 6 common types of mutation which can occur.

Answer 19

– Missense- incorrect amino acid due to single base change
– Nonsense- incorrect sequence causes shortening of protein due to single base change.
– Frame shift- frame shift of one DNA base results in abnormal amino acid sequence.
– Splice site mutations
– Large deletions and duplications
– Translocations

Question 20

How do you take a history to help diagnose whether a cancer is familial or not.

Answer 20

• Include maternal and paternal sides
• At least 3 generations
• Children, siblings, parents, uncles, aunts, nephews, nieces, grandparents, cousins
• Types of cancer, age of diagnosis
• Confirm if possible – medical records, cancer registries, death certificate

Question 21

does sporadic cancer develop at a young or old age

Answer 21

old.

Question 22

does familial cancer develop at a young or old age

Answer 22

young.

Question 23

examples of cancers which are mainly sporadic

Answer 23

cervical and lung

Question 24

are other family members affected in a sporadic cancer

Answer 24

No

Question 25

are other family members affected in a familial cancer

Answer 25

Yes.

Question 26

what type are most adult cancers

Answer 26

epithelial

Question 27

what type are most children's cancers

Answer 27

haematogenous

Question 28

what are the main disadvantages of genetic assessment

Answer 28

* Anxiety/unhappiness – self, children, other relatives * Genetic discrimination * Results may not lead to any change in management * Financial costs to NHS

Question 29

what is the difference between diagnostic and predictive testing

Answer 29

``` diagnostic testing (mutational analysis) usually performed on DNA from a relative affected with cancer to try to identify the familial mutation. If a mutation is identified in the family, predictive testing for the specific mutation may then be offered to other relatives to determine whether or not they are at risk ```

Question 30

what is retinoblastoma

Answer 30

Childhood ocular cancer

Question 31

what is the gene affected in retinoblastoma

Answer 31

Rb gene (TUMOUR SUPPRESSOR)

Question 32

If both the eyes are affected in retinoblastoma, is the cancer likely to be familial or sporadic

Answer 32

familial.

Question 33

what is FAP - familial adenomatous polyposis

Answer 33

Hundreds of bowel polyps (adenomas) from teens onwards

Question 34

what cancer does FAP predispose to is untreated

Answer 34

bowel cancer.

Question 35

what gene is affected in FAP

Answer 35

APC (TUMOUR SUPPRESSOR)

Question 36

What type of inheritance is FAP

Answer 36

autosomal dominant.

Question 37

what is used to diagnose FAP

Answer 37

colonoscopy | total colectomy

Question 38

define polyposis

Answer 38

numerous polyps

Question 39

What type of cancer does Hereditary Non-polyposis colorectal cancer cause

Answer 39

bowel cancer.

Question 40

What type of inheritance is hereditary non-polyposis colorectal cancer

Answer 40

autosomal dominant.

Question 41

what other cancers can you develop if you have hereditary non-poylposis cancer.

Answer 41

endometrial/ovarian/stomach/GU

Question 42

what genes cause hereditary non polyposis colorectal cancer

Answer 42

Mismatch repair genes | MLH1 (50%), MSH2 (40%), MSH6 (10%), PMS1/2 (rare)

Question 43

what criteria is used to diagnose hereditary non-polyposis colorectal cancer

Answer 43

Amsterdam criteria

Question 44

What is the Amsterdam criteria.

Answer 44

* One member diagnosed with colorectal cancer before age 50 years * Two affected generations * Three affected relatives, one of them a first-degree relative of the other two * FAP should be excluded-using histology. * Tumours should be verified by pathologic examination

Question 45

benefits of colonscopic screening in HNPCC | What is it used to detect

Answer 45

Removal of polyps/early detection of cancer improves survival

Question 46

when should patient with HNPCC start to have colonoscopies.

Answer 46

Patients with HNPCC should have colonoscopy ~every 18-24 months from age ~25

Question 47

HNPCC preventative surgery

Answer 47

Prophylactic colectomy is not usually recommended | However, women may consider hysterectomy +/- BSO

Question 48

what are BRAC1 and BRAC2 involved in

Answer 48

DNA repair.

Question 49

what inheritance is breast cancer

Answer 49

autosomal dominant.

Question 50

Inheritance of BRAC1/BRAC2 (tumour suppressor genes) increases the risk of which cancers other than breast

Answer 50

. prostate, melanoma, male breast cancer

Question 51

What can BRAC1/BRAC 2 carrier do.

Answer 51

* Breast screening – annual MRI 30-50, annual + mammography from ~35-40 * Risk-reducing mastectomies +/- reconstruction * Risk-reducing BSO (ovarian screening probably no use) * Lifestyle changes * Pharmacological prevention studies

Question 52

what genes does Li Fraumeni syndrome affect

Answer 52

P53 mutations

Question 53

what inheritance is Li Fraumen

Answer 53

autosomal dominant.

Question 54

what cancers does Li Fraumeni cause

Answer 54

Breast, sarcoma, brain, adrenocortical, leukaemia

Question 55

why could Li Frumeni patient avoid radiotherapy

Answer 55

induces other cancers

Question 56

what medication may potential prevent polyps | blood thinner

Answer 56

apirin)

Question 57

signs of FAP

Answer 57

CHRPE (flat, pigmented spot within the outer layer of the retina), desmoid tumours, osteomas (benign tumour of new piece of bone growing)

Question 58

what cancer does RB gene predispose to except retinoblastoma

Answer 58

osteosarcoma.