Genetic lectures 1-3

Question 1

% of breast and ovarian cancer which is sporadic, hereditary and breast cancer family clusters

Answer 1

Breast - 15/20% clusters and 5-10% hereditary

ovarian is 5-10% hereditary

Question 2

colorectal cancer % of each cause

Answer 2

65-85% sporadic
10-30% familial
5% HNPCC, FAP

Question 3

oncogenes problem

Answer 3

problem leads to uncontrolled cell growth

Question 4

where do oncogenes, DNA repair genes and tumour suppressor genes work in the cell cycle?

Answer 4

oncogenes between G1 and G0
TSG - between GO and S
DNA - between S and G2

Question 5

Germline mutations

Answer 5

mutation in sperm or egg which are heritable
cancer family syndromes
all cells affected in offspring

Question 6

somatic mutations

Answer 6

occur in non germline tissues and are nonheritable

eg breast

Question 7

oncogene mutations

Answer 7

1st mutation leads to accelerated cell division and 1 mutation is sufficient for role in cancer development

Question 8

Example of diseases with oncogene mutations

Answer 8

leukaemia oncogene ABL - BCR ABL fusion protein

retinoblastoma

Question 9

tumour suppressor genes mutation

Answer 9

susceptible carrier and 2nd mutation or loss of normal genes leads to cancer

Question 10

HNPCC - what is the mutation?

Answer 10

mismatch repair genes

Question 11

HNPCC

Answer 11

excess of CRC, endometrial, ovarian, gastric and urinary tract cancers
adenoma carcinoma sequence

Question 12

Tumours in HNPCC

Answer 12

proximal colon

Question 13

BRCA 1 and 2 and lifetime risk of breast and ovarian ca

Answer 13

breast: 60-80%
secondary primary breast: 40-60%
ovarian: 20-50%

Question 14

Males and BRCA2

Answer 14

prostate and breast cancer

Question 15

when to suspect hereditary cancer syndrome?

Answer 15

autosomal dominant 
early age at diagnosis 
more than 2 close relatives 
multiple and rare cancers - bilateral 
characteristic pattern eg breast or ovarian

Question 16

Cancer genetics process

Answer 16

obtain detailed accurate FH 
confirm diagnoses of cancer 
risk estimation 
counselling 
interventions eg signs/lifestyle/prophylaxis 
genetic testing

Question 17

Breast cancer surveillance options

Answer 17

breast awareness
early clinical surveillance 5yrs less than 1st age of cancer in the family
- annual breast exams
- mammography 2yrs 35-40, 1yr 40-50
high risk mammography 18monthly from 50-64
MRI at highest risk

Question 18

prophylactic mastectomy

Answer 18

removes most but not all breast tissue
decreases breast cancer risks
total removes more than subcutaneous

Question 19

prophylactic oophorectomy

Answer 19

eliminates risk of primary ovarian cancer
peritoneal carcinomatosis may occur
laparascopic, HRT until 50

Question 20

benefits of genetic testing

Answer 20

identifies highest risk
identify non-carriers
early detection and prevention
may relieve anxiety

Question 21

Risks and limitations of genetic testing

Answer 21

does not detect all mutations
sporadic cancer
efficacy for interventions
psychosocial/economic

Question 22

li-fraumenti syndrome

Answer 22

TP53 mutations
soft tissue sarcoma, leukaemia, brain tumour
whole body MRI, breast screening

Question 23

modes of inheritance for multisystem disorders

Answer 23

new mutations or inherited
chromosomal
single gene disorders
multifactorial

Question 24

numerical and structural chromosomal mutations

Answer 24

numerical eg trisomy 21

structural eg translocation

Question 25

single gene disorders

Answer 25

AD AR x-linked

Question 26

multifactorial genetic conditions

Answer 26

polygenic | environmental

Question 27

Common problems of multisystem disorders

Answer 27

variable expression large variety of specialities FH easily missed

Question 28

NF1, TS and mytonic dystrophy inheritance

Answer 28

Autosomal dominant

Question 29

criteria for NF1 diagnosis and how many are needed?

Answer 29

``` café au lait spots - 6 or more neurofibromas axillary freckling lisch nodules, optic gliomas thinning long bone cortex FH ```

Question 30

Further features of NF1

Answer 30

macrocephaly, learning difficulties, epilepsy short stature, noonan look high bp - renal artery stenosis, phaechromocytoma CNS and endocrine neoplasia pseudoarthritis of tibia

Question 31

diagnosis of NF1

Answer 31

clinical

Question 32

managing NF1

Answer 32

annual review - bp, spine, eyes, tibia

Question 33

Genetics of NF1

Answer 33

variable expression - 17q (tumour suppressor genes) | 50% due to new mutation

Question 34

NF1 and NF2

Answer 34

NF2 has acoustic neuroma, CNS and spinal tumours | chromosome 22

Question 35

classic triad of TS

Answer 35

epilepsy learning disability skin lesions

Question 36

genes in TS

Answer 36

1 in 700 - AD variable expression TSC1 and TSC2 almost full penetrance - on scans

Question 37

Clinical features of TS

Answer 37

multisystem variable expression - asymptomatic 40% learning difficulty seizures - infantile spasms, myoclonic

Question 38

Other features of TS

Answer 38

skin lesions eg depigmented macules, angiofibromas, shagreen patches, fibrous plaques forehead, subungual fibroma kidney - cysts and angiomyolipomata phakomas in eye - benign unless on macula rhabdomyomas in heart

Question 39

Screening at risk of TS relatives

Answer 39

skin, woods lamp, nails, cranial MRI, echo, Renal USS

Question 40

myotonic dystrophy genetics

Answer 40

AD, CTG repeat on chromosome 19, anticipation

Question 41

myotonic dystrophy signs

Answer 41

bilateral late onset cataracts muscle weak, stiff, myotonia decreased motivation, IBS, DM heart block

Question 42

Why are adults referred to genetics?

Answer 42

``` diagnosis predictive testing carrier test cascade screening FH fetal loss or recurrent miscarriage ```

Question 43

what prediction testing can and must not be used for

Answer 43

usable to prevent or treat disease 3rd parties no access children only tested if it benefits them counselling

Question 44

SOD enzyme

Answer 44

catalyses intracellular superoxide radicals conversion which damage nerve cells motor neurons express this enzyme highly

Question 45

Where are SO1-3 found and what metals?

Answer 45

``` 1= cytoplasm and 3 = extracellular --> Cu, Zn 2 = mitochondria --> manganese ```

Question 46

Huntingtons genetics

Answer 46

CAG expansion

Question 47

advantages of predictive testing

Answer 47

uncertainty removed if -ve = concerns reduced if +ve = plan, surveillance, inform children

Question 48

disadvantages of predictive testing

Answer 48

if +ve = remove hope, when?, risk to offspring | if -ve = survivor guilt