Session 9 - Neoplasia 3 Flashcards
What are the 5 leading behavioural and dietary risk factors related to developing cancer?
30% of cancer deaths are caused by
- High body mass index
- Low fruit and vegetable intake
- Lack of physical activity
- Tobacco use
- Alcohol use
What type of cancer does the carcinogen 2-napthylamine cause and what did research into this carcinogen show?
This mutagen causes bladder cancer.
It showed that sometimes there is a long delay between carcinogen exposure and malignant neoplasm onset
The risk of cancer depends on the carcinogen dosage
Sometimes carcinogens have organ specificity
What does the Ames test show in cancer?
This test showed that initiators are mutagens and promoters cause prolonged proliferation in target tissues.
What is progression? (with regards to cancer)
This is where a monoclonal neoplasm will give rise to a number of mutations.
What are pro-carcinogens?
These are substances that can act as carcinogens but do not become carcinogens until they are metabolised by cytochrome P450 enzymes in the liver.
What are complete carcinogens?
These are carcinogens that act as both initiators and promoters.
What are the two different types of radiation (that cause cancer)
ultraviolet light and ionising radiation. UV only penetrates the skin whereas ionising radiation can knock the electrons off of atoms which is highly damaging.
What are the mechanisms in which an infection can be carcinogenic?
- Infections can directly affect the genes that control cellular growth
- Can cause chronic tissue injury and regeneration acts as a promoter for any pre-existing mutations or else causes new mutations from DNA replication errors.
How is the human papilloma virus a precursor to the formation of CIN and invasive cervical cancer?
HPV expresses E6 and E7 proteins that inhibit p53 and pRB protein function respectively, both of which are important in cellular proliferation.
What is Knudson’s two hit hypothesis?
This suggests that for neoplasia to occur you need ‘2 hits’ as such. So in the case of familial cancers (such as dominantly inherited retinoblastoma) - the first hit would be the germline mutation and the second hit would be the somatic mutation
In sporadic cancers - both of the mutations would need to be somatic mutations.
How many alleles need to be inactivated on tumour suppressor genes and proto-oncogenes for neoplastic growth?
- Tumour suppressor genes need 2 alleles to be inactivated as they act like brakes on tumour growth so therefore to not function they need to be completely switched off.
- oncogenes however promote tumour growth and only one allele needs to be inactivated in order to promote tumour growth as it is just the mere modification of the proto-oncogene.
Which oncogene do you find in a third of all malignant neoplasms? What does this oncogene do?
RAS - this is a small G protein that relays signals into the cell and eventually pushes the cell past the cell cycle restriction point.
Mutant RAS encodes a protein that is always active
What is the RB gene?
It is a tumour suppressor gene that when both alleles are inactivated means that individuals are likely to develop a retinoblastoma due to the unrestrained passage through the restriction point of the cell cycle.
What kind of substances can proto-oncogenes encode?
- Growth factors - eg. PDGF
- Growth factor receptors - eg. Her2
- Plasma membrane signal transducers - eg. RAS
- Intracellular kinases - eg. BRAF
- Transcription factors - eg. MYC
- Cell cycle regulators - eg. Cyclin D1
- Apoptosis regulators - eg. BCL2
What is xeroderma pigmentosum?
An autosomal recessive condition due to mutations in one of 7 nucleotide excision repair genes.
These patients are very sensitive to UV damage and develop skin cancer at a very young age.
