Genetics - Inherited cancers Flashcards
Are inherited cancers germline or somatic mutations?
Germline. They’re present in the egg/sperm and are heritable.
Somatic are non-heritable
What are the 3 gene types involved in cancers?
Oncogenes
Tumour Suppressor Genes
DNA mismatch genes
Mainly the last 2 in heritable cancers
What do each of the 3 gene types do?
Oncogenes regulate growth
Tumor suppressor genes prevent mutations
DNA mismatch repair genes repair base pair mismatches
How does a germline mutation start?
Founder gets the mutation in their egg or sperm –> Ends up in every cell in their offspring.
2nd generation has it in every cell so 50/50 chance of passing it on in their egg/sperm and so on
What type of gene is mutated in HNPCC (lynch syndrome)?
Mismatch repair genes
How do we clinically spot HNPCC?
Early CRC diagnosis (~45 yrs) predominates in proximal colon
What types of cancer are you at risk of with the BRCA1/2 genes?
60-80% get primary breast cancer
40-60% get a 2nd primary breast cancer
20-50% get ovarian cancer
Men will get more prostate or breast cancer
What features would make us think a cancer patient might have a hereditary cancer syndrome?
2 or more close relatives Early age onset Multiple primary tumours Bilateral or multiple rare cancers Characteristic patterns e.g. breast & ovarian Autosomal dominant pattern
What is involved in a cancer genetics process?
Obtain a family history
Confirm diagnoses of cancer
Estimate patients risk
Genetic counselling (including testing and interventions)
What are the pros of genetic testing?
- Identifies high risk individuals
- Identifies non-carriers in a family
- Allows early detection & prevention
- Can relieve anxiety
What are the limitations of genetic testing?
Can’t detect all mutations
Even if -ve still at risk of sporadic cancer
Can cause psychosocial or economic harm
Intervention efficacy is variable
What kind of screening can we do on someone at risk of familial breast cancer?
Annual breast exams and annual/2yrly mammographs
Moderate risk
- 2 yrs from 35-40
- yrly from 40-50
High risk
-MRI
5 yrs before the earliest age of onset in the family
What kind of screening can we do for someone at risk of familial CRC?
High risk - 2 yrly colonoscopy from 25
Mod risk - colonoscopy at 35 & 55
We can do prophylactic surgery for some familial cancer syndromes such as:
Prophylactic mastectomy - reduces breast cancer to 5% in BRCA1 +ve women
Prophylactic Oophorectomy - eliminates ovarian cancer but peritoneal carcinomatosis can still occur. Also requires HRT till 50.
HNPCC Mutations
mutations in mismatch repair genes
