genetic predisposition to cancer

Question 1

alteration in single/several base(s)

Answer 1

non-functional protein
reduced function
shorten protein due to premature stop codon

causes disease

Question 2

hereditary

Answer 2

strong genetic predisposition

Question 3

familial clusters

Answer 3

polygenic inheritance or genetic susceptibility factors accumulating within family

Question 4

tumours are clonal expansion

Answer 4

tumours are caused by clonal expansion of cell with mutations in its DNA
mutations accumulate
high rate of growth with metastatic potential

Question 5

germline mutations

Answer 5

inherited from single alteration in ova/sperm
present in all cells in offspring
heritable
causes familial cancer syndromes

Question 6

somatic mutations

Answer 6

occur in non-germline tissues
non-heritable
vast majority cancers

Question 7

what part of cell cycle to oncogenes control

Answer 7

first part

Question 8

what part of cell cycle due tumour suppresor genes and DNA repair genes work

Answer 8

second part where we have DNA synthesis

Question 9

oncogenes normally

Answer 9

regulate cell growth

Question 10

oncogene 1st mutation

Answer 10

leads to accelerated cell division

1 mutation sufficient for role in cancer development

Question 11

tumour suppressor genes normally

Answer 11

prevent cancer

Question 12

tumour suppressor genes 1st mut and 2nd mut/loss

Answer 12

1st: susceptible to cancer

2nd/loss: leads to cancer

Question 13

multistep carcinogenesis e.g. colon cancer

Answer 13

normal epithelium which proliferates
adenoma
molecular events accumulate and more dysplasia
carcinoma which can metastasis

Question 14

faulty DNA mismatch repair

Answer 14

main mechanism for familial cancers

mean DNA with mistake is not repair, mistake can persist and trigger multistep process

Question 15

HNPCC/Lynch Syndrome

Answer 15

mutation in mismatch repair genes: germline predisposition to mismatch repair

excess colorectal, endometrial, urinary tract and gastric cancers

Question 16

clinical features HNPCC

Answer 16

early but variable age at CRC diagnosis

tumour site in proximal colon predominates

Question 17

BRCA 1 + 2 assoc cancer risks

Answer 17

breast: 60-80%
2nd 1ry breast: 40-60%
ovarian: 20-50%

Question 18

BRCA2 in men

Answer 18

inc risk prostate and breast cancer

Question 19

autosomal dominant inheritance

Answer 19

each child has 50% chance inheriting mutation
no skipped generations
equally transmitted by men and women

Question 20

when to suspect hereditary cancer syndrome

Answer 20

cancer 2+ close relatives, same side F
early age diagnosis
multiple 1ry tumours
bilateral/multiple rare Ca
characteristic pattern of tumours e.g. breast and ovary
evidence autosomal dominant transmission

Question 21

cancer genetic interventions

Answer 21

• inc awareness symptoms/signs
• lifestyle: smoking, diet, exercise
• prevention: oestrogen, aspirin use
• screening
• prophylactic surgery

Question 22

breast cancer surveillance options

Answer 22

breast awareness
early clinical surveillance 5yrs < age 1st FH Ca
-annual breast exams
-mammography
-MRI highest risk

Question 23

when to do genetic testing for breast and ovarian cancer

Answer 23

all non-mucinous ovarian cancer
triple negative breast cancer under 60 with FH
BCRA under 40

Question 24

genetic tests breast cancer

Answer 24

BCRA 1 and 2
PALB2
PTEN 
P53
CHEK2

Question 25

genetic testing ovarian cancer

Answer 25

BRCA 1 and 2
Lynch genes
RAD51C
RAD51D

Question 26

surveillance for CRC

Answer 26

colonoscopy

• 2yrly from 25 if gene carrier
• high-mod riks 5yrly from 50
• low-mod once 50

also prophylactic aspirin

Question 27

screening for lynch syndrome

Answer 27

IHC for mismatch repair gene proteins

microsattelite instability testing

Question 28

benefits of genetic testing

Answer 28

id highest risk
id non-carriers in families w known mutation
allows early detection and prevention strategies
may relieve anxiety

Question 29

risks/limitations of genetic testing

Answer 29

doesn’t detect all mutations
continued risk sporadic cancer
efficacy of interventions variable
may result in psychosocial/economic harm