We do not know what causes most osteosarcomas. Scientists, however, have found that osteosarcoma is associated with a number of other conditions, which were described in the previous section on risk factors. It is important to remember that most patients with osteosarcoma do not have any known risk factors, and we do not know what causes their cancers at this time. There is nothing anyone could have done to prevent the cancer.

Over the past few years, scientists have made great progress in understanding how certain changes in our DNA can cause cells to become cancerous. A copy of our DNA is in every cell of our body. It carries the instructions for nearly everything our cells do. We usually resemble our parents because they are the source of our DNA. However, DNA affects more than our outward appearance. It influences our risks for developing certain diseases, including some kinds of cancer.

Some genes (parts of our DNA) contain instructions for controlling when our cells grow and divide. Genes that promote cell division and cause cells to live longer than they should, are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. We know that cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes. Some people with cancer have mutations they inherited from a parent; in this situation, all the cells in the body carry the mutation. These are called germline mutations. These mutations increase their risk for the disease. Usually, however, cancer-causing mutations are acquired during life rather than inherited before birth; in this case, the mutation occurs only in the cells that will develop the cancer. These are called somatic mutations.

We know the DNA mutations that cause some inherited forms of osteosarcoma.

The Li-Fraumeni syndrome is caused by inherited mutations that turn off the p53 tumor suppressor gene. These mutations give a person a very high risk of developing one or more types of cancer that include breast cancer, brain cancer, osteosarcoma, and other cancers.

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

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

Although radiation is very useful in treating some forms of cancer, it can also cause cancer by damaging DNA. This is why bones exposed to radiation used to treat another cancer are more likely to develop osteosarcoma in the treated site later in the person's lifetime.

Other DNA mutations have no apparent cause but 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 this copying process is not completely accurate. Scientists still do not know exactly why or how these mutations happen to some people but not to others. Fortunately, cells have ways of "proofreading" DNA copies and repairing any errors. When cells divide shortly after their DNA is damaged, new "daughter cells" may be formed before the original cell has time to repair its DNA damage. Once the cells are formed, it is too late to repair the damage. The result is that cell instructions for growth control can be permanently altered, and a cancer (such as osteosarcoma) may develop. This is why 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 developing osteosarcoma.

Although researchers are making progress in understanding this process, there are still some points that are not completely understood. Hopefully, a more complete understanding will help develop ways to better prevent and treat osteosarcoma.

Last Medical Review: 01/14/2009
Last Revised: 01/14/2009