The exact cause of most bone cancers is not known. However, scientists have found that bone cancers are associated with a number of other conditions, which are described in the section on risk factors. Keep in mind that most people with bone cancers do not have any known risk factors and that the causes of their cancers remain unknown at this time. Research is underway to learn more about these causes.
During the past few years, scientists have made great progress in understanding how certain changes in a person's DNA can cause bone cells to become cancerous. DNA carries the instructions for nearly everything our cells do. We usually look like our parents because they are the source of our DNA. However, DNA affects more than our outward appearance. It may influence 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 are called oncogenes. Others that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA mutations (defects) that activate oncogenes or inactivate tumor suppressor genes. Some people with cancer have DNA mutations that they inherited from a parent. These mutations increase their risk for the disease. Usually, however, DNA mutations are acquired during life rather than inherited before birth.
The DNA mutations that cause some inherited forms of bone cancers are known. The Li-Fraumeni syndrome is caused by inherited mutations that inactivate the p53 tumor suppressor gene. This results in a very high risk of developing one or more types of cancer that include breast cancer, brain cancer, osteosarcoma, and other sarcomas. Inherited defects of the 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.
When children inherit Rb or p53 mutations from a parent, these mutations are present in every cell of their body and, therefore, can be detected by testing DNA of blood cells. Because every person has two p53 and two Rb genes but passes only one of each to their children (the other gene comes from their mate), the odds that a parent will pass their mutated gene on to a child are 1 out of 2.
The majority of bone cancers 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 the patient's 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 as a treatment for other cancers are more likely to develop bone cancer later in the patient'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. But 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, multiple exostoses, and multiple osteochondromas) causing rapid bone growth increase the risk of developing osteosarcoma.
Although scientists are making progress in understanding this process, there are still some points that are not completely understood. As their knowledge increases, they hope to develop ways to better prevent and treat bone cancers