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Define carcinogenesis:

Causes of cancer


The cause of neoplasia is multifactorial. What does this mean? Give some examples:

It means that a combination of intrinsic host factors (heredity, age and gender (especially hormonal)), and extrinsic factors (environment and behavioural) account for cancer risk.


What has caused much of the increased cancer incidence over the last century?

Prolonged lifespan - age is a strong intrinsic factor that accounts for cancer risk.


About 30% of cancer deaths are due to the five leading behavioural and dietary risks. What are they?

1. High body mass index
2. Low fruit and vegetable intake
3. Lack of physical activity
4. Tobacco use
5. Alcohol use


Which behavioural/dietary factor accounts for approximately 25% of all cancer deaths?

Tobacco smoke.


Where has the evidence about cancer risks come from?

Epidemiological and animal studies.


How much of a population's cancer risk is caused by extrinsic factors?



What three lesson about carcinogenesis did epidemiological studies into workers in the dye industry who were exposed to the carcinogen, 2-napthylamine?

1. There is a long delay (sometimes decades) between carcinogen exposure and malignant neoplasm onset
2. The risk of cancer depends on total carcinogen dosage
3. There is sometime organ specificity for particular carcinogens e.g. 3-napthylamine causes bladder carcinoma.


Why is chemical exposure in an industrial setting more important for considering cancer risk than that in a domestic setting?

Cancer risk is dependent on the dose of carcinogen you are exposed to. This is often much higher in an industrial setting (e.g. asbestos, coal, tars, vinyl chloride), though smoking is an exception as high levels can be experienced at home.


In animal experiments is has been shown that the sequence in which carcinogens are administrated is critical. Explain why this is the case:

Some chemical carcinogens, called initiators, must be given first followed by a second class of carcinogens called promoters. This is because initiators are mutagens while promoters cause prolonged proliferation in target tissues. This culminates in monoclonal expansion of mutant cells.


What did the Ames test show?

That initiators are mutagens while promotors cause prolonged proliferation in target tissues.


How does a germline mutation differ from sporadic mutations in generating a monoclonal population of mutant cells?

Germline mutations skip the sporadic stages of initiation and promotion, as by their nature all cells in the body inherit the germline mutation. They therefore get a "head start".


List some classes of mutagenic chemical carcinogens (initiators):

1. Polycyclic aromatic hydrocarbons
2. Aromatic amines
3. N-nitroso
4. Alkylating agents
5. Natural products: aflatoxin (fungi), asbestos (fibrous rock).


How are chemicals that are classified as pro-carcinogens, turned into carcinogens?

They are converted to carinogens by cytochrome P450 enzymes in the liver.


What are 'complete carcinogens'?

Carcinogens that act as both initiators and promotors.


How far does UV light penetrate?

No farther than the skin.


What is radiation? Is it mutagenic?

A type of energy that travels through space. Some forms of radiation are mutagenic.


What is ionising radiation? List some types of ionising radiation:

Radiation that strips electrons from atoms. X-rays and nuclear radiation (alpha-, beta- and gamma- particles) are forms of ionising radiation.


What are the two main main forms of radiation that we are exposed to?

1. UV radiation - sunlight (exposed daily)
2. Ionising radiation: background radon radiation and from medical tests.


What does ionising radiation do to DNA?

It damages DNA bases and causes single and double stranded DNA breaks.


What are the two main ways in which infections are carcinogenic?

1. Directly - affect genes that control cell growth
2. Indirectly - cause chronic tissue injury.


How is chronic tissue injury carcinogenic?

1. The resulting regeneration acts as a promotor for existing mutations
2. Regeneration causes new mutations from replication errors.


Give an example of an infection which directly affects genes that control cell growth:

HPV (human papilloma virus) expresses the proteins E6 and E7 which inhibit p53 and pRB respectively. Both these proteins are important in regulating cell proliferation. It is associated with cervical cancer, as well as some cancers of the vulva, vagina, penis, anus, and oropharynx.


How is hepatitis B and C carcinogenic?

They cause cancer indirectly by causing chronic liver cell injury and regeneration.


Name a bacteria that is carinogenic and its mechanism of action:

Heliocobacter pylori causes chronic gastric inflammation which can lead to gastric cancer.


Name a parasite that can cause cancer:

Parasitic flukes cause inflammation in bile ducts and bladder mucosa, increasing the risk of gastric. cholangio- and bladder carcinomas.


How does HIV infection predispose to cancer?

It suppresses the immune system and allows other potentially carcinogenic infections to occur.


Explain how the two-hit hypothesis explains the difference between retinoblastoma tumours occurring in families and those occurring in the general population:

1. Families: first hit delivered through germline and affected all cells in the body. The second hit was a somatic mutation.
2. General population: No germline mutations therefore requires both hits to be somatic mutations that occur in the SAME CELL.


What types of genes does initiation and promotion need to affect to lead to neoplasm?

Proto-oncogenes and tumour supressor genes.


What are oncogenes?

Abnormally activated versions of normal genes called oncogenes.