Though the origins of most diseases had been relatively easy to determine using early 20th-century technology, the variable and vexing nature of cancer made it much more elusive. Well into the 1970s, it was believed that most cancers were triggered by viral infection. In fact, viruses are responsible for only a small portion of human cancers. Those tumor-causing viruses, however, had one very unusual quality: they contained mutated versions of normal human genes. This led researchers to discover that the roots of most cancers have been in our cells all along.
Oncogenes are Mutant Forms of Normal Genes
In nearly all of the trillions of cells that make up our bodies, the genes that could help tumors form, grow, and spread simply make proteins that help in normal cellular processes. In this normal state, they are called proto-oncogenes. The proteins produced by proto-oncogenes are usually very important in cells’ growth and division. Thus, a mutation in one of these genes can throw off tightly regulated growth mechanisms. When a proto-oncogene is mutated in this fashion, it is then referred to as an oncogene.
The mutation which creates an oncogene can come in several different flavors, but all have one key quality: they increase the impact of the protein produced by the oncogene in the cell. In some cases, a regulatory component of the protein is defective or deleted. In others, the gene itself is normal, but it’s been duplicated in the cell’s genome, resulting in many more copies of the protein in the cell. Because these proteins are typically so vital to growth processes–they are often associated with growth factor receptors, or are transcription factors which activate whole sets of other genes–they can cause serious problems if not tightly regulated.
Luckily, one oncogene is almost never enough to cause a tumor by itself. Since mutation is always a risk, whether through errors in DNA copying, or the effects of environmental mutagens such as UV rays, there are many failsafe mechanisms in place to kill off out-of-control cells.
Oncogenes and Tumor Suppressor Genes
The mutation that creates an oncogene does so by disabling the regulatory mechanisms which hold its protein product in check. Such alterations are referred to as activating mutations, as they result in increased activity of the affected protein. In the case of oncogenes, an activating mutation results in increased pressure on the cell to grow and divide.
But cells have ways of counterbalancing oncogenes. In the most extreme cases, the afflicted cell is capable of triggering its own death if it is going to spiral out of control. The genes responsible for holding wayward growth in check are referred to as tumor suppressors.
Because of the presence of tumor suppressors, the formation of cancer will almost always require multiple mutations. Oncogenes produce unusually active proteins promoting growth, while inactivated tumor suppressors render the cell unable to stop that growth.
This explains why your risk of developing cancer increases with age. By virtue of having lived longer, older people have been subject to more chances for mutation, through internal or environmental causes. Because more mutations have happened as you’ve aged, it’s more likely that multiple key mutations have ended up in the same cell, leading to uncontrolled growth and tumor formation.
Weinberg, Robert A. The Biology of Cancer (2007). Chapter 4: Cellular Oncogenes, Chapter 7: Tumor Suppressor Genes.