Cancer is a complex group of diseases which affect different cells and tissues in the body. It is characterized by the loss of normal cell control which results in unregulated growth, lack of differentiation, and ability to invade local tissues and metastasize.

Cancer is a major cause of illness and death in developed countries. The risk of death from cancer has also been increasing in the less developed countries. As improvements in medical care have reduced deaths from infectious diseases and increased life expectancy, cancer has become the leading cause of death in many societies. For example, according to the American Cancer Society, about one in three people in the USA will develop cancer at some point in their life, and about one in four will die from it. Each year about 500,000 individuals die of cancer, a rate of about one death per minute, and more than one million new cases of cancer are diagnosed annually in the US. Currently more than 10 million individuals are receiving medical treatment for cancer in US hospitals and medical centres.

What are the causes of cancer?

Scientific evidence gathered over the last hundred years has dispelled the superstition, once prevalent, that cancer is a contagious disease. But, despite significant advances in the last decade, its underlying mechanisms are still a mystery.

The link between cancer and genetic mutation was shown early in this century: normal cells mutate into malignant ones because of changes in chromosome constitution.

There are four points which support the idea that cancer has a genetic origin:

1 More than 50 forms of cancer are known to be inherited to one degree or another

2 Some tests detecting mutations have shown that most environmental toxic agents which are called carcinogens are also mutagens.

3 Work with cancer-associated viruses has revealed the presence of some mutant genes, known as oncogenes, that promote and maintain tumour growth.

4 The chromosomal abnormalities found in particular forms of cancer, especially leukemia.

The environment and behaviour can also play a significant role in the genesis of cancer.

The existence of high rates of specific cancers in particular families has been known since early in the 19th century. Many explanations have been offered for this phenomenon, including multiple gene inheritance, environmental agents or even mere chance.

Hereditary forms of cancer

Recent advances in cancer research have provided some clues about the relationship between mutant genes and the cellular events that lead to tumour formation. Experimental evidence suggests that as few as two mutational events may be sufficient to cause a cell to become cancerous (see Figure I). In those forms of cancer that show a heritable predisposition, the first mutation is present in the germ cells and is transmitted genetically. The second mutations are acquired by somatic cells through spontaneous replication errors or exposure to environmental agents that cause genetic damage, resulting in cancer. On the other hand, not all individuals who inherit the first mutation will develop cancer.

If the second mutational event does not occur, then no tumour will develop. Research has focused particularly on two classes of genes in carcinogenesis: tumour suppressor genes which normally function to suppress cell division, and proto-oncogenes which normally promote cell division.

Tumour suppressor genes

Tumour suppressors are detected in the form of chromosomal deletions (or other inactivating mutations) that are tumorigenic. The strongest evidence for their nature is provided by certain hereditary cancers. There is also now evidence that changes in these genes may be associated with the progression of a wide range of cancers. About 10 tumour suppressors are known at present. These genes act at certain points to inhibit cell division. These and or their gene products must be absent or inactive for normal cell division to take place. If tumour suppressor genes become deleted or inactivated by mutation, control over cell division is lost, and the cell can proliferate in unchecked fashion. The example of breast cancer illustrates how mutations in tumour suppressor genes are involved in the development of cancer:

The genetic link to breast cancer

In the USA, the ratio of women getting breast cancer is approximately 1 in 8. It is the most common form of cancer in women: 46,000 women die and 182,000 new cases are diagnosed each year. Epidemiological factors may also be involved in breast cancer, but geneticists have focused on the question - Is there a genetic predisposition to breast cancer? Their answer, for the present, is Yes: though involved in only about 5% of all eases, a particular gene has been identified and located on chromosome 17. It is responsible for susceptibility to a form of breast cancer that appears in the third and fourth decades of life. About one in 200 females inherits this gene, and 80% to 90% of these will develop breast cancer. Besides breast cancer, a gene has been found on chromosome 17 in sufferers from astrocitoma (brain tumours), colon, lung and bone cancers. This finding suggests that there is a mutation on this gene (called p53), and as a result the cells start growing abnormally.

The Future

Investigations into the tumour suppressor genes are an example of the recent progress in molecular aspects of cancer research. A better understanding of molecular carcinogenesis and molecular epidemiology will eventually decrease the quantitative and qualitative uncertainties associated with the current state of cancer risk assessment. It may be possible to immunize patients against their tumours by using these findings about genes-cancer relationships. Indeed, determination of the type and number of mutations in p53 and other cancer-related genes in tissues from ‘healthy’ individuals may allow the identification of those at increased cancer risk and their consequent protection by preventive measures.

Although there have been many and most welcome developments in the diagnosis and treatment of diseases, including cancer, there is a definite and reliably cure only for some of the infectious diseases. However, we firmly believe there are definite remedies for all diseases in the universe except death.

References

HARRIS, ADRIAN L. (1990)
‘Mutant p53-The commonest genetic abnormality in Human Cancer?’ The Journal of Pathology.
HARRIS, CURTIS C. (1993)
‘p53: At the Cross-roads of Molecular Carcinogenesis and Risk Assessment’, Science, 262.
CUMMINGS, M. (1994)
Human Heredity, West Publishing Company, St Paul. Lewm, B. (1994) Genes 5, Oxford University Press, New York.

LEWIN, B. (1994)
Genes 5, Oxford University Press, New York.

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