Cancer is caused by genetic changes called mutations, which occur in the DNA of cells. In the beginning, it perhaps only a single cell that undergoes a mutation. When this cell divides, this property (mutation) is passed on to all the daughter cells, one of which may undergo a further mutation, which in turn is passed on to its progeny, and so on. This permanent genetic change may give a growth advantage to the mutated cell over other cells or enables it to evade the normal controls that regulate a cell. Thus, mutations accumulate and cause the cell to become progressively more aggressive, eventually producing a full-blown cancerous cell that can keep dividing uncontrollably. Some of these cells may detach from the primary site and migrate to other parts of the body where they invade normal tissue (known as metastasis). It is currently thought that about 5-7 successive mutations are required before cancer develops in a cell. Along with mutations there are other non-mutational changes which may occur in the DNA affecting the behaviour of cells.
The importance of environmental factors (such as diet, lifestyle, exposure to ultraviolet radiation or carcinogenic pollutants) in cancer cannot be underestimated. Although cancer is certainly a genetic disease, only a minority of cancer cases arises purely due to heritable genetic changes. Environmental factors play a role in the development of all cancers, even where there is a strong familial predisposition. Genetic variants and environmental factors are not independent, but interact to influence whether cancer will develop or not.
About 2% of cancers are familial and such families may show a very strong hereditary susceptibility to a particular rare type of cancer or cancer syndrome. Affected individuals in these families carry an inherited mutation present in every cell of their body making it more likely for cancer to arise. This cancer-susceptibility is very penetrant i.e. individuals inheriting the faulty gene have a strong likelihood of developing cancer. Some hereditary cancers include breast cancer, ovarian cancer and colorectal cancer. Many hereditary cancer syndromes are extremely rare.
Most cancers have no clear familial clustering, though sometimes an affected person may have one or two relatives affected by the same cancer. In some cases there may be some inherited predisposition to the disease. For most common cancers, an individual with a first-degree relative with the disease will have approximately twice the risk of the general population. The inherited genetic alterations involved are likely to be both common and of very low penetrance.