Two faulty mutated genes will result in a functional problem
Chemical carcinogens
Initiators:long lasting genetic damage, not sufficient to cause cancer – must be followed by a promoter
Promoters:require initiators to have caused damage, time period can vary after initiation
Smoking
> 40 carcinogens, e.g. polycyclic aromatic hydrocarbons –
Can also be present in animal fat (meat), smoked meat and fish
Lung cancer, head and neck cancers, cervical cancer (with HPV)
Aflatoxin (fungus on peanuts)
Liver cancer
Associated with p53 mutations
Common in China
Most liver cancers in the west don’t have p53 abnormality until the later stages
Beta-naphthylamine (chemical dyes)
Bladder cancers
Conjugated in the liver with glucuronic acid – not toxic for too long
Nitrosamines
Food preservatives
Arsenic
Skin cancer
Other carcinogens
Radiation
Causes formation of pyrimidine dimers in DNA
Nucleotide excision repair is eventually overwhelmed
Xeroderma pigmentosa: genetic defect in NER, suffer from numerous skin cancers
CT scanners → leukaemias and thyroid cancers
New scanners use lower dose of radiation
Viruses
HPV: produces E6 and E7
E6 increases destruction of p53
E7 prevents Rb protein from acting - E2F can promote transcription
EBV (glandular fever): responsible for a subset of malignancies including Burkitt lymphoma, B-cell lymphoma, Hodgkin lymphoma and nasopharyngeal carcinoma
Chronic inflammation
Constant lymphocyte reproduction may lead to errors in production → lymphomas
Tissue replicating so often will cause it to become unstable → tumours
Schistosomiasis - squamous cell tumours caused by chronic inflammatory response to parasite
Obesity
Hyperplastic tissue
Cholesterol is analogous to oestrogen → renal cell carcinoma
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