Cancer is a disease caused by unregulated cell growth and multiplication. It is characterised by failure of the regulation of the cell cycle, leading to uncontrolled growth and cell division.
Cancerous cells are defined as those that are dividing uncontrollably and also are able to spread and invade other tissues.
Cancer is one of the most common diseases in the developed world. It can affect almost any cell type.
All cancers, apart from leukaemia (cancer of the bone marrow and blood), result in the growth of masses of abnormal cells known as tumours.
Cancer is caused by a series of mutations in proto-oncogenes and tumour suppressor genes. These genes code for proteins that are important in regulating the cell cycle.
A tumour is an abnormal mass of cells that replicate in an uncontrolled manner.
Tumours are classified depending on their ability to invade other tissue.
- Benign tumours are masses of abnormal cells that do not damage surrounding cells as they are unable to invade other tissue types.
These tumours are usually harmless and are easily removed through surgery. As benign tumours are unable to spread to other parts of the body they are not classified as cancerous.
- Malignant tumours can damage surrounding cells and invade other tissue types, spreading to other parts of the body. These tumours are cancerous.
Metastasis is the spread of malignant tumour cells to other parts of the body. As cancerous cells spread, the cancer becomes harder to treat.
Cancer is caused by a series of mutations in a single cell line (a group of cells that are all descended from a single cell).
The cause of these mutations varies from cancer to cancer.
It is estimated that 90-95% of cancers are caused by environmental factors while 5-10% are genetic. Environmental factors include:
Chemicals: Some chemicals are known to cause DNA mutations. Accumulation of these mutations can lead to cancer. The chemicals in cigarette smoke and asbestos are common examples of carcinogens.
Lifestyle: Poor diet, lack of exercise and obesity increase cancer risk.
Radiation: Exposure to radiation can increase the number mutations in DNA. Ultraviolet radiation is responsible for skin cancer.
Viruses: Viruses account for about 18% of all cancers. The human papilloma virus is responsible for nearly all cases of cervical cancer.
There are two main types of genes involved in the development of cancer: oncogenes and tumour suppressor genes.
- Oncogenes result in unregulated cell division.
A normal cell carries two copies of the proto-oncogene. Proto-oncogenes code for proteins that control cell division in a normal and regulated way.
Mutations or the loss of regulation of these genes can leave them permanently active and the cell begins to divide uncontrollably.
Proto-oncogenes that become permanently active through mutation are called oncogenes.
Only one of the two copies of each proto-oncogene needs to mutate into an oncogene for unregulated cell division to occur and a cancer to develop.
An oncogene arises from a gain of function mutation. It is so named because the mutation leads to permanent or increased expression of a protein.
Oncogenes code for a wide range of proteins, such as trans-membrane receptors and transcription factors.
The development of cancer is a multi-step process involving a series of mutations.
- A cancer usually begins when an oncogene is activated via the mutation of a proto-oncogene. This causes cell replication and division to occur more rapidly.
- Tumour suppressor genes are often inactivated leading to formation of a benign tumour.
- As mutations accumulate in the cell genome, more oncogenes are turned on and more tumour suppressor genes are switched off. This eventually leads to the formation of a malignant tumour.
- These cells are now cancerous; they have the ability to damage surrounding tissue and metastasise (spread to other parts of the body).
Ras (short for "rat sarcoma") is a common proto-oncogene that codes for a signal transducer. This is a cytoplasmic protein which turns on signal pathways leading to cell proliferation (replication and division) and differentiation.
The ras gene commonly undergoes a gain of function mutation to become an oncogene. Permanent expression of ras is found in a quarter of all tumours.
Ras can become an oncogene in two ways:
- A mutation of the actual gene may leave the protein constantly switched on, resulting in uncontrolled cell replication and division.
- A gene amplification results in many copies of the gene becoming present in the chromosome.
This leads to the production of too many ras proteins and also causes uncontrolled cell replication and division.
Tumour suppressor genes code for proteins that inhibit cell division, repair DNA or initiate cell death.
If a tumour suppressor gene mutates, the functional protein is no longer produced and the above processes no longer occur. As a result, the cell survives and carries on dividing when it should not.
Tumour suppressor gene mutations are classified as loss of function mutations. This means that the gene's function is either lost or reduced. The protein the tumour suppressor gene codes for may become less effective, or it may not be produced at all.
If proto-oncogenes are the "green light", allowing the cell to divide, tumour suppressor genes are the "red light", preventing cell division.
Loss of function mutations are normally recessive mutations, meaning that two mutated copies must be present for an effect on cell function.
One functioning tumour suppressor gene can still produce enough protein for the cell cycle to continue normally.
TP53 is a tumour suppressor gene which codes for the p53 tumour suppressor protein. Loss-of-function mutations in the TP53 gene are found in half of all human cancers.
If the p53 protein is knocked out (no longer produced) or damaged (e.g. through mutated) cells will continue to grow and divide. These cells are at a much higher risk of becoming cancerous.
For the p53 protein to be knocked out, both copies of the TP53 gene must mutate.
Some people inherit just one functional copy of the TP53 gene. As a result they have a much higher risk of developing cancer.