Genetic Predisposition to Cancer Flashcards
From what types of mutations can cancer arise?
Somatic mutations (non-inheritable) Germline mutations (egg/sperm; passed on; every cell in child)
What three types of genes can cause cancer?
Oncogenes
Tumour suppressor genes
DNA damage-response genes
How can oncogenes cause cancer?
- formed from proto-oncogenes
- accelerate cell division
- one mutation needed to lead to cancer
What is the function of proto-oncogenes?
Regulation of cell growth and differentiation
Give an example of an oncogene and a cancer it can cause
RET can lead to multiple endocrine neoplasia
What is the function of tumour suppressor genes?
- inhibit the cell cycle
- promote apoptosis
- mutations in both needed to lead to cancer (‘two-hit hypothesis’)
Give an example of a tumour suppressor gene and a cancer it can cause when defective
BRCA1 can lead to breast cancer
APC can lead to FAP
What is HNPCC?
Hereditary non-polyposis colorectal cancer
What is microsatellite instability?
Phenotype of DNA damage-response genes:
Microsatellite DNA fragments can be detected using PCR and indicate MMR isn’t working properly
What is the function of DNA damage response genes?
- repair of DNA errors (during replication/synthesis…)
- mutations in both needed to lead to cancer
What is another name of DNA damage response genes?
MMR - mismatch repair genes
Give an example of a MMR/DNA damage-response gene and a cancer it can cause when defective
MLH1 can lead to HNPCC
Give two other possible genetic causes of cancer
- autosomal recessive disorders (e.g. MYH associated polyposis/MAP)
- multiple modifier genes of lower genetic risk
What are the features of heritable retinoblastoma?
- bilateral tumours
- 20% family history
- diagnosis at < 1 year old
- every cell has the mutation, therefore increased risk of osteosarcoma/melanoma
What are the features of non-heritable retinoblastoma?
- unilateral tumour
- no family history
- diagnosis at around 2 years old
- no increased risk of second primary cancers
Give some environmental risks of developing breast cancer
- ageing
- diet
- exercise
- family history…
Mutations in what genes can cause breast cancer?
- BRCA1
- BRCA2
- PTEN
- TP53
- many undiscovered genes
What is the normal function of BRCA1?
Codes for a tumour suppressor protein that repairs damaged DNA (example of a tumour suppressor gene)
What is the normal function of BRCA2?
DNA repair by homologous recombination
Give some risks of developing colorectal cancer (CRC)?
- ageing
- history of CRC/adenomas
- IBS
- high fat/low fibre diets
Name three types of colorectal polyposis
FAP (familial adenomatous polyposis)
AFAP (attenuated FAP)
MAP (MYH associated)
What are the clinical features of HNPCC?
- early diagnosis age
- tumours throughout colon
- extracolonic cancers also present
What are the clinical features of FAP?
- high penetrance for adenomas
- extracolonic cancers
- CHRPE often present
- untreated polyposis leads to a 100% chance of developing cancer
What are the clinical features of AFAP?
- later onset
- few adenomas
- no CHRPE present
- upper GI lesions
- associated with mutations in the APC gene
