Familial Cancer Syndromes Flashcards
What is the proportion of people who will get cancer? What proportion will die?
1/3 …. 1/4 will die
What do gatekeeper cells do (basic)?
Monitor and control mutation and cell death, prevent accumulating mutations
What do caretaker cells do (basic) ?
Improve the genomic stability, repair mutations
Landscaper cells do what?
Control the stromal environment
% chance of cancer with gatekeeper faults?
> 95%`
% chance of cancer with caretaker faults?
70%
% chance of cancer with landscaper faults?
10-20%
Sporadic defects have a high chance of turning to cancer, true or false?
False low rate ~5%
Loss of function of tumour suppressor genes does what?
Increases risk of certain cancers eg BRCA1
Oncogenes gaining function or mutation does what?
Increases risk of cancers Growth factors etc
Classic example of two hit hypothesis?
Retinoblastoma
How many tumour suppressor genes must be knocked out on each allele in order to create malignancy? (what type of malignancy)
Both genes on both alleles (sporadic cancers)
Inherited cancers are different in the way the tumour suppressor genes are organised, how?
One allele is already knocked out only need one more hit
Most cancer syndromes show what type of inheritance|?
Autosomal dominant 50/50
A few cancers are autosomal recessive give three examples!
MYH polyposis
Fanconi anaemia
Ataxi telangiectasia
What is the proportion of children to inherit a recessive cancer ?
1/4
Recessive cancers are often sporadic too, why?
Possible generation skipping
How many generations at least do you take in a history?
3
Onset at a younger age and multiple primary tumours is classic of what?
Familial cancers
Irradiation for Retinoblastoma can increase the risk of what cancer?
Osteosarcoma
Bilateral cases of Retinoblastoma are almost always due to what?
Germline mutations
Familial Adenomatous polyposis is inherited how?
Autosomal dominant
Is FAP high risk if untreated?
Yes ~100% will get cancer if untreated
Other features of FAP can include what?
CHRPE, Desmoid tumours and osteomas
What is the risk of bowel cancers in hereditary non polyposis colorectal cancer? and when?
60-80% mid 20’s onwards
HNPCC is associated with which genes?
Mismatch repair
Which criteria is used to diagnose HNPCC?
Amsterdam
When should patient with HNPCC start bowel surveillance?
from age 25 every 1-2 years
Women with HNPCC might consider what?
Hysterectomy +- BSO
What are BRCA1 and BRCA 2 involved in ?
DNA repair
BRCA1 or 2 confers higher ovarian cancer risk?
BRCA1
Approx risk of breast cancer with BRCA genes?
80%
Breast screening for those with BRCA genes consists of what?
MRI yearly 30-50 and mammography from 40 or post menopause
What mutation does Li Fraumeni syndrome affect?
P53 rare
Risk of cancer at 40 and lifetime risk?
At 40 is 50% and close to 100% lifetime
Li Fraumeni syndrome causes what type of cancers?
Breast sarcoma brain leukaemia
Li Fraumeni syndrome is often associated with problems in which age?
Children
