Primary bone cancer is a rare disease that begins when cells in the bone grow out of control, forming a tumor. This is distinct from metastatic bone cancer, which starts elsewhere in the body—such as the breast or lung—and spreads to the skeleton. Since cancer involves changes to the genetic material of cells, many question whether bone cancer is an inherited condition. The answer involves distinguishing between mutations acquired during a lifetime and those passed down through generations.
Primary Types of Bone Cancer
Primary bone cancers are a type of sarcoma categorized based on the cell type where the tumor originates. These types often affect distinct age groups and parts of the skeleton, suggesting varied underlying causes.
Osteosarcoma is the most frequently diagnosed primary bone cancer, developing in cells that form new bone tissue. It primarily affects teenagers and young adults, often near the growth plates of long bones like the thighbone (femur) or shinbone (tibia). Ewing sarcoma, the second most common type, typically arises in the bone or surrounding soft tissue, frequently affecting the pelvis, ribs, or long bones. This type is also seen most often in children and adolescents.
Chondrosarcoma is the third major type, developing from cartilage cells. It is most prevalent in adults aged 30 to 60, often located in the pelvis, shoulder blades, or upper arm and leg bones.
Genetic Influence: Inherited vs. Sporadic Cases
Distinguishing between two types of gene changes, or mutations, helps answer whether bone cancer is inherited. The vast majority of cases are sporadic, arising from acquired mutations that occur randomly in a single cell during a person’s lifetime. These mutations are present only in the cancer cells and cannot be passed down to children.
An inherited, or germline, mutation is present in every cell of the body, having been passed from a parent. These inherited changes significantly increase a person’s risk of developing cancer, often at a younger age. However, they do not guarantee that cancer will develop, and less than 10% of bone cancer cases are linked to an inherited genetic predisposition.
The most common gene changes leading to bone cancer are acquired somatic mutations that affect genes controlling cell growth or suppressing tumors. Because inherited factors play a minor role and primary bone cancer is rare, most people who develop it have no known family history or identifiable genetic risk factor.
Specific High-Risk Genetic Syndromes
Although rare, a few specific inherited conditions are associated with an increased risk of developing bone cancer. Children with hereditary retinoblastoma, caused by a mutation in the RB1 tumor suppressor gene, have an increased risk of later developing osteosarcoma.
Li-Fraumeni syndrome (LFS), caused by an inherited alteration in the TP53 gene, also elevates the lifetime risk for several cancers, including osteosarcoma. Other rare inherited conditions, such as Rothmund-Thomson Syndrome (RTS) and Werner syndrome, involve mutations in DNA repair genes and are linked to an increased predisposition for osteosarcoma.
People with Multiple Exostoses Syndrome, an inherited disorder characterized by benign cartilage growths on the bones, have an increased risk of developing chondrosarcoma. These syndromes involve germline mutations that predispose an individual to cancer, but they account for only a small fraction of all primary bone cancer diagnoses.
Non-Hereditary Risk Factors
Factors contributing to sporadic bone cancer are acquired or environmental, not inherited through DNA. One established risk is prior exposure to high-dose radiation therapy, particularly in childhood, which can increase the risk of developing osteosarcoma in the treated area years later. The risk from medical imaging, such as X-rays or CT scans, is considered very low compared to therapeutic radiation exposure.
Certain pre-existing, non-cancerous bone conditions also increase the risk for some types of primary bone cancer. Paget disease of the bone, which causes abnormal bone breakdown and regrowth, can increase the chance of developing osteosarcoma in older adults. Rapid bone growth during adolescence is also a factor for osteosarcoma, which may explain its peak incidence in teenagers.