SYNERGY AND SIGNATURE
Synergistic effects are important
- Aflatoxin (a mycotoxin produced by Aspergillus species) is a serious risk factor for liver cancer only in combination with hepatitis infection
- Radon causes lung cancer - and the association is far stronger in smokers than in non-smokers
- Asbestos causes lung cancer, especially in smokers
Signature - mutational spectra in tumours
Certain kinds of DNA damage produce certain kinds of base-change, and so might leave a ‘signature’ in the mutations that result. Mutations in the p53 gene (See chapter 2 Cancer genes) have been analysed in thousands of tumours.
- UV light induces mainly C → T transitions at dipyrimidine sites in DNA.
In skin tumours from xeroderma pigmentosum (XP) patients, half had point mutations in p53, and all were at dipyrimidine sites. 61% were CC → TT - a very rare mutation in internal tumours. Xeroderma pigmentosum
- Aflatoxin seems to have a very characteristic effect, changing AGG to AGT at p53 codon 249; this was found in 58% of liver tumours in China.
Unfortunately, most other mutational signatures are not unique.