clinical cancer genetics

Question 1

germline mutations

Answer 1

hereditary
inform future cancer risks
inform treatment decisions
provide info for family members

Question 2

somatic mutations

Answer 2

acquired
inform treatment decision
provide reassurance for family and future kids

Question 3

cancer statistics

Answer 3

65% cancer = sporadic
25% = familial cancer
10% = high risk cancer genes

Question 4

multifactorial/polygenic familial risk

Answer 4

larger percentage of familial cancers than high risk cancer predisposition gene
no single high risk gene identified
lower risk genetic factors than environmental factors
no current testing available
increased screening available for some cancer types in high risk individuals

Question 5

why identify patients with increased genetic predisposition to cancer

Answer 5

1. inform medical management and surgical options
2. reason for why developed cancer
3. informs patients about future cancer risk
4. informs relatives about cancer risk

Question 6

tumour > germline testing

Answer 6

cancer patients are now being offered large cancer gene panel sequencing of their tumour
if there’s disease causing change in cancer predispositon gene when testing tumour = might be in germline > blood test offered

Question 7

multifactorial risk assessment

Answer 7

larger percentage of familial cancers
no routine genetic testing
family history of proxy
screening, prevention and early detection

Question 8

describe cancer predispositon genes

Answer 8

vast majority are inherited in autosomal dominant fashion so 50% chance of passing on to child
sometimes autosomal recessive, both parents carry and passed onto child

Question 9

outcomes of diagnostic testing

Answer 9

no disease carrying variant identified manage on family history/personal diagnosis

variant of uncertain significance identified = analyse variant

disease causing variant identified = manage gene protocol/offer cascade. screening to relatives

Question 10

describe BRCA1 +2 genes

Answer 10

most frequent monogenic cause for hereditary breast cancer
20% of familial breast cancer
contribute 2% to overall cancer
involved in DNA repair and regulation of cancer

Question 11

carrier management

Answer 11

screening
risk-reducing surgery
chemo prevention for BRCA2 carriers
male BRCA2 carriers recommended to have annual PSA test

Question 12

describe lynch syndrome

Answer 12

womb and cervical cancer
1/440
1-3% of all bowel cancers
mutation in MLH1/MSH2/MSH6/PMS2

can do tumour test for mutations 
screening 
chemoprevention 
research 
cancer management 
family matters