Characteristics of cancer
Uncontrolled proliferation of cells gives rise to a tumour. Tumour cells are characterised by
- Unlimited growth in culture (normal cells will only go through a limited number of cell divisions, and then senesce and die).
- Loss of normal controls on cell division, such as contact inhibition
Cell signalling pathways are disrupted.
- Genetic instability; aneuploidy
Cancer is multi-factorial, involving:
- Inherited factors
- Environmental factors - including lifestyle, diet
- Medical history (infections, injury, treatment)
- Chance: mutations affect genes at random
Figure Cancer incidence rises steeply with age. The shape of the curve is consistent with a need for several independent events to occur at random. The older we are, the greater the chance that all will have occurred. If cancer incidence rises as the 4th or 5th power of age, then there must be 4 or 5 independent events. These random events are mutations.
Mutations are permanent changes in the genetic information. They can arise from very rare mistakes in replication (incorporation of the wrong base, or incorporation of wrong number of bases, namely slippage or they can be caused by:
- exogenous agents (radiation, chemicals)
- endogenous agents (alkylation, oxidation)
- Most DNA damage is repaired before replication
- Only damage that is still unrepaired when cells replicate DNA results in permanent changes in DNA sequence
- Cells with a large amount of damage tend to die through apoptosis
- Most mutations are harmless, because they occur in non-coding DNA
- Mutations in coding regions do not necessarily change the function of the protein
- Only mutations in certain genes result in increased risk of cancer
'Points to remember: First
Mutations are not the whole story ...
epigenetic factors are important. One definition of epigenetic factors: factors that change the expression of a gene (not the gene sequence) and that is passed on to the daughter cells.
Examples of changes are DNA methylation and histone hypo-acetylation.
Discussion question: How can epigenetic factors influence cancer development?
Tumour promotion is also dependent on cell proliferation.
Some chemicals that are not themselves carcinogenic increase the yield of tumours induced by previous treatment with a carcinogen. They are often known as tumour promoters. Many environmental chemicals have this property e.g. phenobarbital, phorbol ester (TPA). Also, some endogenous agents - notably bile acids. Often they act by inducing cell proliferation.
- Cell proliferation is essential to the process of carcinogenesis.
- An increase in proliferation rate leads to clonal expansion.
- If a cell in which a potentially tumorigenic mutation has already occurred is involved in clonal expansion, whatever the cause, progression to cancer will be made more likely/accelerated, simply because of the increased number of cells and of replication cycles.
- Proliferation rate is increased by tissue injury. In animal experiments, damage to liver following treatment with carcinogen increases the likelihood of cancer.