Genes and Cancer – Using genes to treat cancer
All cancers are the result of genetic mutations, although only 5-10% of these mutations are heritable – that is, passed on through families. The majority of cancers (90-95%) are not inherited and cannot be predicted, nor can their exact cause be identified. However, advances in genetic science are revealing that a heightened susceptibility to some cancers can be inherited.
This knowledge is enabling physicians to identify people at higher risk of developing cancer and to prescribe screening regimes and other measures to increase their chances of avoiding the disease or detecting its onset as early as possible. Researchers are also developing ways to use the genetic basis of cancer as a means to treat the disease.
Cancer – cells growing out of control
The cells that make up all living things continually renew themselves through the process of cell division. When a cell divides into two new cells, the DNA that makes up the genes of the original cell is copied. Normally, the two new cells are formed, each with a complete and exact copy of that DNA, but mistakes in copying can occur. Most are corrected naturally or have no ill effect. However, if many small mutations accumulate over time they can significantly alter the way a cell behaves.
Mutations can occur due to ageing, and environmental factors such as UV radiation from sunlight, poor diet, tobacco smoking, and exposure to some chemicals.
The types of mutations most likely to lead to cancer are those which occur in genes that regulate the process of cell division and gene copying. If a mutation occurs in one of these control genes, cell division in subsequent generations of cells is likely to be more loosely regulated. This could lead to more mutations, eventually leading to cells growing and dividing abnormally. Then they become one of the more than a hundred kinds of cancer which share one trait: cells multiplying out of control to supplant or destroy healthy tissue. Often, these cancer cells become “immortal” – they multiply out of control, lose their programming to die like normal cells, or both.
There are three types of genes which are collectively known as cancer control genes. When these genes are mutated, they may no longer be able to prevent the development of cancer, or they may actively promote it.
Tumour suppressor genes act as brakes on uncontrolled cell growth. If mutations render these genes inactive, a tumour may result. Oncogenes, when mutated, can accelerate cell division to the point where a tumour results.
Mismatch repair genes find and repair mistakes that occur when genes are copied during cell division. If these genes are mutated so that they no longer perform their corrective function, further mutations in genes may result, leading to tumour formation.
It is important to note that cells do not usually become cancerous due to a single mutation or loss of function in one control gene. Cancer is due to the build-up of mutations in a number of different control genes. This usually makes cancer development slow and complex.
What is a predisposition and what does it mean?
Mutations in control genes can be passed from parents to their children. Although cancers sometimes appear to run in families, this may be due to coincidence (because cancer is a relatively common disease) or because family members are exposed to the same environmental influences. There may not be a common inherited mutation.
An inherited mutation in a control gene increases the risk that cancer will develop but it does not mean that cancer will certainly develop. If subsequent generations of cells do not accumulate further mutations in their critical control genes then cancerous growth can be averted.
How can I know if I have inherited a predisposition?
Genetic testing involves the examination of a person’s DNA or the proteins and enzymes the DNA produces (see Genetic Testing). Results of these tests may confirm or eliminate suspicion of a genetic mutation, or abnormality in a protein product. They may show that a person is predisposed to developing a particular disorder. It is also possible to determine the probability that a person will develop a disorder, such as cancer, based on the presence of the mutation, long before any symptoms are apparent.
The effects of a faulty gene are determined by factors such as the type of mutation, the location of a mutated gene in a person’s genome, and its impact on the enzyme or protein that the gene causes a cell to produce.
Although genetic testing for predisposition genes can be useful for some cancers, it is not always of benefit. It is also essential to undergo suitable counselling before undertaking genetic testing.
Using genes to treat cancer
As our understanding of the genetic basis of cancer has improved, so has our ability to modify genes in cells, giving rise to opportunities to use gene therapy to treat cancer.
Research in this area has progressed to the stage where small-scale clinical trials involving human subjects have been conducted around the world. Australian researchers have conducted gene therapy trials involving patients suffering from melanoma, prostate and lung cancer, generally recording significant but inconsistent improvements in survival rates.
All gene therapies are currently experimental, and most have not progressed beyond trials using animal subjects. Clinical trials of gene therapies for cancer involving human subjects have so far been limited to early-phase trials involving small numbers of subjects who are usually suffering from advanced stage cancer. All clinical trials that involve the introduction of genetic material into human subjects must be considered by the Gene and Related Therapies Advisory Panel (GTRAP) prior to approval by a Human Research Ethics Committee.
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