GENETICS

Question 1

what percentage of breast and ovarian cancer is hereditary?

Answer 1

5-10%

Question 2

what percentage of breast cancer is due to family clusters?

Answer 2

15-20%

Question 3

list the causes of dereditary susceptibility to colorectal cancer…

Answer 3

FAP (1%), sporadic (65-85%), familial (10-30%), HNPCC (5%)

Question 4

key factors of germline mutations

Answer 4

inherited from a single alteration in egg or sperm, heritable, cause cancer family syndromes

Question 5

what is looked for in leukaemia genetics

Answer 5

translocation and bra-abl (oncogene) fusion

Question 6

Retinoblastoma caused by…

Answer 6

rb1 gene 2 copies

Question 7

colon cancer - mutlistep carcinogenesis process overtime

Answer 7

loss of apc > activaiton of kras > loss of 18q > loss of tp53 > other alterations

Question 8

details of lynch syndrome/ HNPCC

Answer 8

mutaiton mismatch repair genes, excess of colorectal endometrial, urinary tract, ovarian and gastric cancers, carcinoma sequence for polyp formation

Question 9

what are the features of HNPCC

Answer 9

tumor site in the proximal colon, asprin often used for prevention

Question 10

cancer frisks in lynch syndrome

Answer 10

endometrial, colon, stomach, ovarian, biliary tract, urinary tract

Question 11

BRCA1 and 2 associated cancers…

Answer 11

breeast (60-80%), ovarian (20-50%), males have an increased ricks of prostate cancer and breast cancer especially with the BRCA2 gene

Question 12

draw an autosomal dominant inheritance mendelian flowchart (pedigree chart)

Answer 12

theres no skipped generations, each child has a 50% chance of inheriting the mutation, it Is equally transmitted by men and women (dominant, high penetrance syndrome)

Question 13

when to suspect a hereditary cancer syndrome

Answer 13

cancer in 2< close relatives on the same side of the family,

early age diagnosis,

multiple primary tumours,

bilateral of multiple rare cancers,

evidence of autosomal dominant transmission

Question 14

what is the process of genetic consulatation?

Answer 14

fhx, confirm cancer, risk estimation , counselling, give interventions

Question 15

what is the age women are screened at

Answer 15

xray mammography at 50yo

Question 16

what can be done to reduce the risk of breast cancer

Answer 16

prophylactic mastectomy, oophorectomy

Question 17

surveilance for crc

Answer 17

use a colonoscopy, give prophylactic asprin if a gene carrier

Question 18

Genetic testing for Lynch Syndrome

Answer 18

IHC for mismatch repair gene proteins or microsatellite instability testing (MSI)

Question 19

Benefits, Risks, and Limitations of Genetic Testing

Answer 19

Identifies highest risk, Identifies non-carriers in families with a known mutation, Allows early detection and prevention strategies, May relieve anxiety. Does not detect all mutations, Continued risk of sporadic cancer, Efficacy of interventions variable, May result in psychosocial or economic harm.

Question 20

what is Li-fraumini syndrome

Answer 20

germline mutation TP53

Question 21

is the breast cancer gene dominant or recessive?

Answer 21

mutations in the BRCA1 and BRCA2 genes are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person’s chance of developing cancer.

Question 22

neurofibromatosis type 1 (NF1)

Answer 22

autosomal dominant, prevelance 1/2500-3500

Question 23

how can you disagnose NF (sx’s)

Answer 23

2 or more of: café du lait spots, neurofibromas, axillary freckling, lisch nodules (specks in the iris), optic glioma, thinning of the long bone cortex, fhx.

Question 24

further sx’s

Answer 24

macrocephaly, short stature, dysmorphic features (noonan look), learning difficulties, epilepsy, scoliosis, pseudoarthritis of the tibia, raised bp due to renal artery stenosis or phaeochromocytoma, neoplasia (cns optic gliomas, or endocrine)

Question 25

genetics of nf1

Answer 25

autosomal dominant, 17q gene (tumour supressor gene), 50% due to new mutaitons (usually parental in origin (from the dad))

Question 26

what are the main features of nf2?

Answer 26

acoustic neuromas (bilateral), cns and spinal tumours, few CAL spots. The nf2 gene is on chromosome 22

Question 27

Tuberous sclerosis (TS)

Answer 27

incidence 1/7000 newborns, autosomal dominant.

Question 28

what is the triad of TS

Answer 28

epilepsy, learning difficulties, skin lesions (austistic features, infantile spasms and myoclonic seizures)

Question 29

what are the genetics of ts?

Answer 29

autosomal dominant, variable expression, 3 genes both on different chromosomes both cause ts - TSC1 and TSC2

Question 30

other features of ts

Answer 30

skin lesions (depigmented macules, angiofibromas, fibrous plaque forehead, shagreen patches, ungual fibromas). Kidney cysts and angiomyolipomata, phakomas in the eye (benign unless on the macula), rhabdomyomas in the heart.

Question 31

how can you screen for ts?

Answer 31

skin signs, retinal examination, crainal MR scan, retinal ultrasound, echo.

Question 32

myotonic dystrophy clincial features

Answer 32

bilateral late-onset cataract, muscle weakness (effects distal muscles, facial muscle and the diaphragm the most), stiffness, myotonia, low motivation, bowel problems, DM, heart block, death post-anaesthetic risk if not monitored, congenital myotonic dystrophy.

Question 33

genetic features of myotonic dystrophy

Answer 33

autosomal dominant, caused by a CTG repeat, this repeat gets more severe with each generation.

Question 34

Amyotrophic lateral sclerosis…

Answer 34

sporadic, 10%familial, Progressive muscle weakness, wasting and increased reflexes (ie upper and lower neurone signs), Limb and bulbar muscles involved. Caused by superoxide dismutase (SOD)

Question 35

What are the clinical features of huntingtons disease

Answer 35

movement disorder - chorea, athetosis, myoclonus, rigidity. Cognitive changes - poor planning & memory - subcortical dementia (executive function), NOT classical dementia, Personality change - Irritable, Apathetic, loss of empathy, ‘A different person’, disinhibition, self centred, Psychiatric disease - depression, paranoia, psychosis. CAG expansion, adult onset, Autosomal Dominant