Do We Know What Causes Osteosarcoma?

Researchers have found that osteosarcoma is linked with a number of other conditions, which were described in What Are the Risk Factors for Osteosarcoma? But the cause of most osteosarcomas is not clear at this time.

Scientists have learned how certain changes in our DNA can cause cells to become cancerous. DNA is the chemical in each of our cells that makes up our genes – the instructions for nearly everything our cells do. We usually look like our parents because they are the source of our DNA. But DNA affects more than how we look. It influences our risks for developing certain diseases, including some kinds of cancer.

Some genes (parts of our DNA) control when our cells grow, divide to make new cells, and die. Genes that help cells grow, divide, or stay alive are called oncogenes. Others that slow down cell division or make cells die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes.

Some people inherit DNA mutations (changes) from a parent that increase their risk of cancer. In this situation, all of the cells in the body carry the same gene change. These are called germline or inherited mutations. Usually, however, cancer-causing changes are acquired during life rather than inherited before birth. In this case, the change occurs only in the cells that will develop the cancer. These are called somatic or acquired gene changes.

Inherited gene changes

Some inherited DNA mutations cause syndromes that are linked with an increased risk of osteosarcoma. For example:

The Li-Fraumeni syndrome is usually caused by inherited mutations that turn off the TP53 tumor suppressor gene. These mutations give a person a very high risk of developing one or more types of cancer, including breast cancer, brain tumors, osteosarcoma, and other cancers.

Inherited changes in the retinoblastoma (RB1) tumor suppressor gene increase the risk of developing retinoblastoma, a type of eye cancer that affects children. Children with this gene change also have an increased risk for developing osteosarcoma.

If you are concerned you or your child might possibly have an inherited gene change, talk with your doctor about whether genetic testing might be helpful. You can also read more about this in our document Genetic Testing: What You Need to Know.

Acquired gene changes

Most osteosarcomas are not caused by inherited DNA mutations. They are the result of gene changes acquired during the person’s lifetime. These changes are present only in the cancer cells and are not passed on to children.

Although radiation therapy is very useful in treating some forms of cancer, it can also cause cancer by damaging DNA. This is why people who get radiation therapy to treat another cancer are more likely to later develop osteosarcoma in the treated site.

Other DNA changes have no clear cause. They may result from random errors that occur when cells reproduce. Before a cell divides, it must copy its DNA so that both new cells have the same set of instructions. Sometimes mistakes are made during this copying process. Cells that are dividing quickly are more likely to create new cells with mistakes in their DNA, which increases the risk that a cancer such as osteosarcoma may develop. This may be why some normal situations (such as the teenage growth spurt) and diseases (such as Paget disease of bone) that cause rapid bone growth increase the risk of osteosarcoma.

Other than radiation, there are no known lifestyle-related or environmental causes of osteosarcoma, so it is important to remember that there is nothing people with these cancers could have done to prevent them.

Researchers now understand some of the gene changes that occur in osteosarcomas, but it’s not always clear what causes these changes. As we learn more about what causes osteosarcoma, hopefully we will be able to use this knowledge to develop ways to better prevent and treat it.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: April 18, 2014 Last Revised: January 27, 2016

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