Neoplasia 3 Flashcards
Give some intrinsic factors for the cause of cancer
Heredity
Age
Gender
Chronic inflammation
Define carcinogenesis
Cause of cancer
Give some extrinsic factors for cancer risk
Smoking Alcohol Lack of exercise Chemicals Infection Radiation Diet -high BMI -low fruit and veg
What do initiators and promoters do?
Initiators are mutagens
Promoters cause prolonged proliferation in target tissue
What are pro-carcinogens?
Chemicals that are only converted to carcinogens by the cytochrome P450 enzymes in the liver
What are complete carcinogens?
Carcinogens that act as both initiators and promoters
What does ionising radiation do to DNA?
Damages DNA bases
Causes single and double strand DNA breaks
How do infections cause cancer?
Affect genes that control cell growth
Cause chronic tissue injury where the resulting regeneration either acts as a promoter for any pre-existing mutations of causes new mutations from DNA replication errors
How does HPV act as a direct carcinogen?
Expresses E6 and E7 proteins that inhibit p53 and pRB protein function, both of which are important for cell proliferation
How do hep B and C act as carcinogens?
They are indirect carcinogens
Cause chronic liver cell injury and regeneration
How does HIV act as a carcinogen?
Indirectly
Lowers immunity allowing other potentially carcinogenic infections to occur
Conditions for sporadic retinoblastoma to occur?
Both hits need to be somatic mutations and to occur in the same cell. (Not inherited)
How is familial cancer inherited?
First hit delivered through the germline and affects all cells. The second hit is a somatic mutation
What are tumour suppressor genes? What changes must occur for cancer to occur?
Genes that inhibit neoplastic growth
Both alleles of the tumour suppressor gene need to be inactivated, explaining why two hits are needed
What are oncogenes? What changes must occur for cancer to occur by these?
Genes that enhance neoplastic growth
Abnormally activated versions of proto-oncogenes
Only one allele of each proto-oncogene needs to be activated to favour neoplastic growth
What is RAS and what does it do?
The first human oncogene to be discovered
RAS proto-oncogene encodes a small G protein that relays signals to the cell that eventually push it past the cell cycle restriction point
What role does mutant RAS have in cancer?
Mutated in approx a third of all malignant neoplasms
In mutants, the protein is always active so there are constant signals pushing it past the restriction point.
What is xeroderma pigmentosum?
Mutation in genes that affect nucleotide excision repair. Cannot repair damage caused by UV.
Sensitive to UV damage and develop skin cancer at a young age
Autosomal recessive
What happens in familial breast carcinoma?
BRCA1 or BRCA2 genes are affected
They are important for repairing double strand DNA breaks
What type of genes does hereditary non-polyposis colon cancer affect?
DNA mismatch repair genes
What is genetic instability?
Accelerated mutation rate found in malignant neoplasms
Due to abnormal chromosome segregation during mitosis and the mutations in genes for excision repair, mismatch repair or genes repairing double strand DNA breaks.
What is the adenoma-carcinoma sequence?
When something begins as a benign adenoma, but progresses to a carcinoma. This is because most malignant tumours require alterations affecting a combination of multiple tumour suppressor genes and proto-oncogenes.
Mutations accumulate
What is progression?
The steady accumulation of multiple mutations
What are the stages of the evolution of cancer?
Initiation
Promotion
Progression
What are the six hallmarks of cancer?
Self-sufficiency in growth signals
Resistance to stop growth signals
No limit on the number of times a cell can divide (cell immortalisation)
Sustained ability to induce new blood vessels (angiogenesis)
Resistance to apoptosis
The ability to invade and produce metastases
What is the enabling characteristic of cancer?
Genetic instability
Give a summary of the model of cancer pathogenesis
Somatic cells exposed to environmental carcinogens which are initiators or promoters
They culminate in a monoclonal population of mutant cells
Inherited mutations in the germline can be present
Some of these clones harbour mutations affecting a PO or a TS gene.
During progression, cells acquire further activated oncogenes or inactivated TS genes, including ones that cause genetic instability
Results in a population of cells that have acquired a set of mutations that produce all of the hallmarks of cancer
