Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes

Cells normally grow in a controlled way, guided by genes. Cancer begins when cells become abnormal and start to grow out of control. This often happens because of changes in certain genes that control how cells grow, divide, and fix damage.

Our bodies are made up of trillions of cells, which must work together to keep us healthy. Our cells divide to make new cells to help the body grow or to replace cells that have died. At the same time, cell growth and division need to be controlled, so the cells don’t grow too much and crowd out the cells around them.

Cell growth and division are controlled by the genes on our chromosomes, which are long strands of DNA arranged in specific patterns inside the cell. Changes in these genes can disrupt normal cell growth and might lead to cancer.

The main types of genes that play a role in cancer are:

• Oncogenes
• Tumor suppressor genes
• DNA repair genes

Cancer is often the result of changes in more than one of these types of genes.

Oncogenes

Proto-oncogenes help control normal cell growth and division. When a proto-oncogene changes (mutates) or becomes too active, it can become an oncogene. When this happens, the cell can start to grow out of control and survive when it shouldn’t. This might lead to cancer.

Two examples of common oncogenes are:

• HER2. This gene makes a protein that promotes cancer growth. It is found in some cancer cells, such as some breast and ovarian cancer cells. If breast cancer is HER2 positive, it usually means there are too many copies of the HER2 gene, which can promote cancer growth.
• The RAS family of genes. These genes make proteins that help cells communicate with each other, grow normally, and die when they are supposed to. Changes in these genes can turn healthy cells into cancer cells.

Oncogenes can be created or turned on (activated) in different ways. For example:

Tumor suppressor genes

Tumor suppressor genes are normal genes that slow down cell division or tell damaged cells to die when needed (apoptosis or programmed cell death). These genes help protect against cancer. When they don't work properly, cells can grow out of control, which can lead to cancer.

Some inherited changes in tumor suppressor genes can run in families and increase the risk of certain cancers, but most changes happen during a person’s lifetime and are not inherited.

For example, the TP53 gene is an important tumor suppressor gene. It makes a protein called p53 that helps control cell division. Rare, inherited changes in TP53  can cause Li-Fraumeni syndrome, a condition that increases the risk of several types of cancer in families.

Changes in TP53 are more commonly found in people without an inherited cancer syndrome. These changes are found only in the cancer cells, not in other cells in the body, and can’t be passed on to a person’s children.

DNA repair genes

When a cell divides, it must copy all its DNA, which is a complex process that can sometimes make mistakes. DNA repair genes fix mistakes in DNA. Or, if mistakes can’t be fixed, these genes trigger the cell to die to prevent problems.

If a DNA repair gene doesn’t work properly, mistakes can build up and sometimes affect other genes, allowing cells to grow out of control. Changes in these genes can either be inherited from a parent or happen during a person’s lifetime.

For example, the BRCA1 and BRCA2 genes help repair DNA. People who inherit certain changes in one of these genes have a higher risk of some types of cancer, particularly breast and ovarian cancer among women. But changes in these genes can also occur in people who did not inherit them.