Causes of Cancer

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The billions of cells that make up a tumour are descended from a single cell that has found a way to escape the normal controls of its growth. This loss of control is caused by damage of the genetic material in the cell, specifically the long, coiled chains of deoxyribonucleic acid (DNA) found in the chromosomes. Such damage can arise during cell division, be induced by environmental agents, or be inherited. Regardless of how the damage is caused, genetic changes and the abnormal growth pattern that they promote are passed on to a cell's progeny (its daughter cells) as the cell divides.

Still, a single damaging genetic event is not enough to convert a healthy cell to a cancer cell. Evidence shows that several accidents must occur to the DNA of one cell for it to become cancerous. In many cases this is a slow process that takes years.

This section begins by explaining the genetic accidents that can give rise to cancer. It then describes various agents in the environment that can induce these changes. Finally, the inherited genetic alterations that predispose an individual to cancer are discussed.

Cells are constantly faced with the decision of whether to proliferate (through cell division), differentiate (by expressing specialized properties that distinguish one tissue or organ from the others), or die. Involved in these decisions are a small number of genes — about 100 of the tens of thousands of genes that make up the human genome. Genes are encoded in the DNA molecules of the chromosomes, which are found in the cell nucleus. A gene can be thought of as a recipe that the cell follows to make a protein, each gene providing directions for a different protein.

The genes that regulate the growth of cells can be divided into two categories: proto-oncogenes, which encourage cell growth, and tumour suppressor genes, which inhibit it. Many of the agents known to cause cancer (chemicals, viruses, and radiation) exert their effects by inducing changes in these genes or by interfering with the function of the proteins encoded by these genes. Mutations in proto-oncogenes tend to overstimulate cell growth, keeping the cell active when it should be at rest, whereas mutations in tumour suppressor genes eliminate necessary brakes on cell growth, also keeping the cell constantly active.

The normal cell is able to repair such genetic damage through its DNA repair mechanisms, such as the so-called mismatch repair genes, whose normal function is to identify and repair defective DNA segments that arise in the normal course of a cell's life. However, if the cell's repair mechanisms are faulty, mutations will accumulate, and genetic damage that has not been repaired will be reproduced and passed to all daughter cells whenever the cell divides. In this way malfunctioning DNA repair machinery contributes to the genesis of some cancers.

When a normal cell senses that its DNA has been damaged, it will stop dividing until the damage has been repaired. But when the damage is massive, the cell may abandon any attempt at repair and instead activate a suicide program called apoptosis, or programmed cell death. The life of a cell can be prolonged for a number of reasons; for example, an excess of molecules that prevent the suicide program from occurring may be present, or the molecules that trigger the apoptotic process may be defective.

Significant prolongation of a cell's life increases the chances that it will accumulate mutations in its DNA that transform the cell. Thus, the failure of a cell to die when it should is another factor that can contribute to carcinogenesis (the development of cancer).

Each of the cancer-causing genetic changes summarized above — mutated proto-oncogenes and tumour suppressor genes, defective DNA repair mechanisms, and failure to trigger apoptosis — is described in more detail below. Alternatively, the reader may proceed directly to the section Cancer-causing agents for a review of the most important carcinogens and their mechanisms of action.