Neoplasia 3 Flashcards
What are the 5 leading behavioural and dietary risk factors for cancer?
High BMI Low fruit and veg intake Lack of physical activity Tobacco use Alcohol use
What percentage of cancer risk do we attribute to the environment?
85%
What are the 3 main categories for extrinsic carcinogens?
Chemicals
Radiation
Infections
What is 2-napthylamine?
Dye
Causes bladder cancer
What did the dye industry end up proving about cancer?
There is a long delay between carcinogen exposure and malignant neoplasm onset
Risk of cancer depends of total carcinogen dosage
There is sometimes organ specificity for particular carcinogens
What does the Ames test show?
Initiators are mutagens
Promoters cause prolonged proliferation in target tissues
Culminates in monoclonal expansion of mutant cells
What type of carcinogens are present in cigarette smoke?
Polycyclic aromatic hydrocarbons
What type of carcinogens are in dye?
Aromatic amines
What type of carcinogens can be generated by the stomach?
N-nitroso compounds
What type of carcinogens is vinyl chloride?
Alkylating agents
How are procarcinogens converted to carcinogens?
Cytochrome P450 enzymes in the liver
What is a complete carcinogen?
One that acts as an initiator and promoter
What is radiation?
Any type of energy travelling through space
What does ionising radiation do?
Strips electrons from atoms
What direct DNA damage can be caused by radiation?
Altered bases
Single/double strand DNA breaks
How is indirect DNA damage caused by radiation?
free radical formation
How can infections be directly carcinogenic?
Affects genes that control cell growth
How can infections be indirectly carcinogenic?
Cause chronic tissue injury
Resulting regeneration acts as a promoter or may cause new mutations
Which cancer is HPV strongly linked to?
Cervical cancer
How does HVP act as a direct carcinogen?
Expresses E6 and E7 proteins
E6 inhibits p53
E7 inhibits pRB protein function
Helicobacter pylori increases risk of …
Gastric carcinoma
Describe the RAS proto-oncogene
Encodes a small G protein that signals to push the cell past the cell cycle restriction point
Mutated in approx 1/3 of all malignant neoplasms
Describe the RB gene
Restrains cell proliferation by inhibiting passage through the restriction point
Inactivation of the RB gene allows unrestrained passage through restriction point
Name some of the many things that proto-oncogenes can encode
Growth factors Growth factor receptors Signal transducers (RAS) Intracellular kinases Transcription factors Cell cycle regulators Apoptosis regulators
What is xeroderma pigmentosum?
Autosomal recessive condition
Mutations in DNA repair genes
Cannot perform nucleotide excision repair
Patient very sensitive to UV damage
What is hereditary non-polyposis colon cancer syndrome?
Mutation affects one of several DNA mismatch repair genes
Autosomal dominant
Associated with colon carcinoma
Which genes are linked to familial breast carcinoma and what are their usual functions?
BRCA1 and BRCA 2
Usually important for repairing double stranded DNA breaks
What do we call the genes that maintain genetic stability?
Caretaker genes (A class of tumour suppressor genes)
What is cancer progression?
A steady accumulation of multiple mutations
What are the 6 hallmark cellular behaviours for cancer cells?
Self sufficiency in growth signals
Resistance to anti-growth signals
No limit to number of times a cell can divide
Sustained ability to induce new blood vessels
Resistance to apoptosis
Ability to invade and produce metastases
What is Burkitt’s lymphoma?
B cell lymphoma Associated with Epstein-Barr virus (EBV) and malaria Activation of an oncogene MYC gene Most commonly affects children
What is familial adenomatous polyposis?
Mutations in APC gene
Rare
Autosomal dominant
Numerous adenomas develop at an early age - almost inevitable progression to adenocarcinomas
Most cases of hepatocellular carcinoma are secondary to something. What can those things be?
Viral HepB or HepC
Metabolic toxins (aflatoxin/alcohol)
Endogenous toxins (haemochromatosis)
Chronic liver disease
