MOD Neoplasia III Flashcards
Give 3 intrinsic factors in neoplasia pathogenesis
Heredity
Age
Gender
Give 3 extrinsic factors in neoplasia pthogenesis
Environment
Behaviour
Give 5 behavioural risk factors. Proportion of cancer death?
Smoking Alcohol High BMI Low fruit/veg Lack of exercise 30%
Give 3 extrinsic carcinogens. Proportion of cancer risk?
Chemical
Infection
Radiation
85%
Give three factors of chemical carcinogens causing cancer, with example.
Long delay between exposure and malignant neoplasm formation.
Dose dependent, greater dose, more neoplasm.
Can be organ specific.
E.g. 2-naphthalamine causes bladder cancer.
Give 3 chemical carcinogens
Polycyclic aromatic hydrocarbons -lung, bladder, skin Aromatic amines -bladder cancer. Alkylation agents
What are initiators?
Mutagenic agents that cause carcinogenic mutation in either TSGs or proto-oncogenes.
What are promoters? Give examples
Induce tumours in initiated cells by promoting proliferation and increasing incidence of further mutation.
E.g. Hormones, local tissue responses, growth factors
What are pro carcinogens?
Metabolised in the liver by the cytochrome P450 system to a carcinogenic agent.
What is a complete carcinogen?
Acts as both intiator and promoter
Describe how radiation causes mutation.
Direct DNA damage
- altered bases
- double stranded breaks
Indirect DNA damage
- free radicals
Describe nucleotide excision repair and base excision repair
Damaged DNA excised and replaced by DNA polymerase.
Nucleotide - 30 bases due to Uv damage
Base - 1-5 bases due to oxidative damage
Describe the different exposures to types of radiation
UV radiation form sunlight
Ionising radiation from radon, medical tests
Nuclear radiation
Alpha, beta, gamma
How does HPV cause cancer? Which?
HPV expresses two proteins E6/E7 that inactivate TSG proteins p53 and pRb.
This results in cell speeding through cycle by activating cyclins and CDK with no restriction checking, and apoptosis inhibition.
Activate telomerase.
Cervical carcinoma
How can causes of neoplasia be divided?
Intrinsic and extrinsic factors
How do Hep B and C cause cancer?
Indirect carcinogens
Cause chronic hepatocyte injury.
This leads to increased cell division, which results in increased mutation risk.
Hepatocellular carcinoma
How does helicobacter pylori cause cancer
Indirect
Chronic gastric inflammation
Increased risk of gastric carcinoma
How does Epstein Barr cause cancer?
Viral genes disrupt normal proliferation.
Increased acquired mutation risk
Hodgkin’s lymphoma
How does HIV lead to cancer
Reduced immunity
More mutagenic infections
How do parasitic flukes cause cancer
Inflammation of bile ducts/bladder Increased regeneration Increased mutation risk Cholangiocarcinoma Bladder carcinoma
Describe the 2 hit hypothesis using Retinoblastoma example
In familial retinoblastoma, one hit is inherited in the germ line. Thus only one hit must be acquired in the TSG for inactivation.
In sporadic retinoblastoma, no hit is inherited so both hits must be acquired.
A hit is a procarcinogenic mutation
Give the difference in mutations required for neoplasm in TSGs and Protooncogenes
TSG
Both alleles must be mutated to inactivate the TSG which acts as breaks on the cell cycle to suppress growth
protoongenes
Normal gene that becomes oncogene by one mutation resulting in activation enhancing neoplastic growth.
What is RAS
Proto oncogene that encodes a small G protein that pushes cell past the restriction point in the cell cycle.
Mutant RAS is always active, constantly producing a signal to pass the restriction point
What is RB
A TSG that inhibits cell proliferation by inhibiting passage through restriction point.
Inactivation of both RB alleles allows unrestrained passage rough cell cycle.
