20 Carcinogenesis Flashcards
What are the categories of human carcinogens? (6).
Chemicals. Infectious agents. Radiation. Minerals. Physiological. Chronic inflammation.
Give two examples of chemical carcinogens:
PAH.
Nitrosamines.
Give two examples of infectious carcinogens:
Helicobacter pylori.
Human papilloma virus.
Give two examples of mineral carcinogens:
Asbestos.
Heavy metals.
Give two examples of physiological carcinogens?
Oestrogen.
Androgens.
Give two examples of carcinogens resulting from chronic inflammation:
Free radicals.
Growth factors.
What does aflatoxin cause?
Liver cancer.
Where do X-rays cause cancer?
Bone marrow.
Where does HBV cause cancer?
Liver.
Where does HPV cause cancer?
Cervix.
Define a carcinogen:
Any agent that significantly increases the risk of getting cancer.
Differentiate between initiators, promoters, and complete carcinogens:
Initiator: chemically modifies DNA.
Promoter: induces proliferation.
Complete: an initiator and promoter.
What does mutation induction (initiation) require? (2).
Chemical modification of DNA.
Replication of modified DNA and mis-incorporation of DNA polymerase.
How doe promoters contribute to carcinogenesis? (2).
Stimulate two rounds of DNA replication required for mutation fixation.
Stimulate clonal expansion of mutated cells.
Name a complete carcinogen:
UV light.
How are tumour suppressor genes commonly inactivated?
Aberrant methylation of gene promoter region.
What do mutations in oncogenes lead to?
Gain of function.
What do mutations in tumour suppressor genes lead to?
Loss of function.
Name four direct acting carcinogens:
Oxygen radicals.
Nitrosamines.
UV light.
Ionising radiation.
What are procarcinogens?
Carcinogens which require enzymatic activation before they can interact with DNA.
Name two pro carcinogens:
Aromatic amines.
Polycyclic aromatic hydrocarbons (PAH).
Benzopyrene is a pro-carcinogen, how does it become a carcinogen?
Reaction with P450 mixed function oxidases and epoxide hydrolase.
Becomes BPDE.
What does BPDE stand for?
Benzo pyrene 7,8-diol, 9,10-epoxide.
What is the NER pathway?
What do defects in it lead to?
Nucleotide-excision repair. Xeroderma Pigmentosum (UV sensitivity).
What is the ATM gene involved in?
What do defects in it lead to?
Recombinational repair.
Ataxia telangiectasia.
What is Ataxia telangiectasia?
Autosomal recessive disorder with x100 cancer risk.
What does the ATM gene product interact with?
Tumour supressor genes such as TP53 and BRCA1.
What do defects in mismatch repair genes lead to?
HNPCC.
Why do the same levels of carcinogen exposure lead to different levels of cancer?
Genetic variation in metabolic enzymes, DNA repair genes and detoxification/excretion.
Which carcinogens are present in tobacco smoke? (5).
Polycyclic aromatic hydrocarbon: benzopyrene. Acrolein. Nitrosamines. Radioactive lead + polonium. Heavy metals: cadmium, chromium.
Where does alcohol cause cancer? (7).
Mouth. Oesophagus. Pharynx. Larynx. Breast. Bowel. Liver.
How does alcohol cause cancer? (5).
Converted to acetaldehyde (direct damage).
Increases levels of oestrogen + testosterone.
Increases uptake of carcinogens in GI tract.
Reduces folate levels (accuracy decreases).
Kills surface epithelium (proliferation).
How does oestrogen cause cancer? (2)
Stimulates cell division.
Directly induces DNA damage.
What are the risk factors for breast cancer related to oestrogen exposure? (7).
Oral contraceptives. Hormone replacement therapy. Alcohol consumption. First pregnancy >30 years. Early menarche. Late menopause. Post menopausal obesity.
How does chronic inflammation cause cancer? (2)
Initiation: free radical release by immune cells.
Promotion: growth factor induced cell division.
What proportion of cancer deaths are due to preventable causes?
> 50%
