Session 10 Flashcards
What factors contribute to increased cancer risk?
Intrinsic - heredity, age and gender
Extrinsic - environment and lifestyle. 85% of a populations cancer risk. Includes chemical, radiation and infections.
What are the 5 leading behavioural and dietary risks of cancer that lead to 30% of cancer deaths?
High BMI Low fruit and veg intake Lack of exercise Tobacco use Alcohol use
What did malignant neoplasms caused by 2-napthylamine from the dye industry show?
There is a long delay between exposure and onset
The risk of cancer depends on carcinogen dosage
There is sometimes organ specificity for particular carcinogens (bladder for 2-napthylamine)
What does the Ames test show and how is it carried out?
Shows initiators are mutagens and promotors cause prolonged proliferation in target tissue.
A rat liver extract containing cytochrome P450 is added to a salmonella strain requiring histidine. When added to a media with minimal histidine, the salmonella only grows when a possible mutagen is added. This suggests the mutagen causes mutations.
How and where are chemical pro carcinogens converted into carcinogens?
By cytochrome P450 in the liver
What is the name given to carcinogens that act as both initiators and promoters?
Complete carcinogens
List the clinically important types of radiation
Ionising - alpha particles, beta particles, gamma rays and X rays
Electromagnetic - gamma rays, X rays and UV rays
Nuclear - alpha particles, beta particles and gamma rays
How can radiation damage DNA?
Directly - altered bases or single/double strand breaks
Indirectly - generate free radicals
How can infections cause neoplasms?
Directly - they can affect genes that control cell growth.
Indirectly - they can cause chronic tissue injury, where regeneration acts as either a promoter for any pre-existing mutation or causes new mutations when DNA replicates.
How does HPV act as a carcinogen?
It is a direct carcinogen because it expresses E6 and E7 proteins that inhibit p53 and pRb respectively, both of which are important in cell proliferation. p53 normally causes apoptosis and pRb normally inhibits the cell cycle. Hence cells infected with HPV abnormally survive and proliferate.
HPV is linked to cervical carcinoma.
How do the Hepatitis B and C viruses act as carcinogens?
They are indirect carcinogens that cause chronic liver cell injury and regeneration.
Give an example of a bacterium and a parasite that are indirectly carcinogenic
Helicobacter pylori - chronic gastric inflammation
Parasitic flatworms - cause inflammation of the bile ducts and bladder mucosa, increasing the risk of carcinoma
How does HIV act as a carcinogen?
Acts indirectly by lowering immunity and allowing potentially carcinogenic infections to occur
Describe the two hit hypothesis for tumour suppressor genes using retinoblastoma as the example
This tumour can occur sporadically or in members of the same family.
For familial retinoblastoma (dominant inheritance), the first hit is through the germline and affected all the cells in the body. The second hit was a somatic mutation - affecting 1 in 10million retinal cells. Usually bilateral retinoblastoma.
Sporadic retinoblastoma has no germline mutation so requires both hits to be somatic mutations IN THE SAME CELL. Usually unilateral.
Why do tumour suppressor genes need two hits but proto-oncogenes only need one?
Both alleles for the tumour suppressor gene need to be INACTIVATED but only one of each allele for the proto-oncogene needs to be ACTIVATED.
How can the restriction point be deregulated by both activated oncogenes and inactivated tumour suppressor genes?
The RAS proto-oncogene encodes a small G protein that signals to push the cell past the cell cycle restriction point.
The Rb gene restrains cell proliferation by inhibiting passage through the restriction point (tumour suppressor gene). Both alleles need to be inactivated.
What substances can proto-oncogenes and tumour suppressor genes encode?
Growth factors, growth factor receptors (oncogene HER-2), plasma membrane signal transducers, intracellular kinases, transcription factors (oncogene c-myc), cell cycle regulators and apoptosis regulators.
What is xeroderma pigmentosum?
Autosomal recessive condition due to a mutation in one of the genes that causes DNA excision repair. These patients are very sensitive to UV damage and can develop skin cancer at a young age.
What is hereditary non-polyposis colon cancer (HNPCC)?
Autosomal dominant condition resulting in a mutation in one of the DNA mismatch repair genes.
What do BRACA1 and BRACA2 genes do and what neoplasm are they associated with?
They repair double stranded DNA breaks. Familial breast carcinoma.
What is the function of caretaker genes?
They are tumour suppressor genes that maintain genetic stability and reduce the mutation rate.
Describe the colonic adenoma-carcinoma sequence
A benign colonic adenoma accumulates multiple mutations, sometimes over decades, to become a colon carcinoma. This is cancer progression. Hence cancer evolves by initiation, promotion and progression.
What are the 6 hallmarks and one enabling feature of a fully evolved malignant neoplasm?
Self sufficiency in growth signals
Resistance to growth stop signals
No limit on the number of times the cell can divide (cell immortalisation)
Ability to produce new blood vessels (angiogenesis)
Resistance to apoptosis
Ability to invade and produce metastases (exclusive to malignant)
What is the main neoplasm associated with Epstein Barr virus?
Burkitt’s lymphoma
