The exact cause of multiple myeloma has not been identified. Researchers, however, have gained a greater understanding of how specific changes in DNA can cause plasma cells to become cancerous.

Some forms of cancer are caused by DNA mutations that “turn on” oncogenes (genes that speed up cell division) or “turn off” tumor suppressor genes (genes that slow down cell division or cause cells to die at the right time). Researchers have determined that irregularities of some oncogenes develop early in the course of plasma cell tumors. Mutations in other oncogenes are more likely to be discovered in myeloma after bone marrow relapse. Mutations in tumor suppressor genes are associated with spread to other organs. 

Myeloma cells also have irregularities in their chromosomes, which are pieces of DNA and protein that regulate cell growth and metabolism. Normal human cells contain 46 chromosomes. Many myeloma cells, however, have parts of chromosome 13 missing. Known as a deletion, this abnormality appears to make the myeloma more aggressive and resistant to treatment.  

Another form of DNA abnormality is a translocation. A translocation is the transfer of DNA from one chromosome to another. This abnormality can turn on oncogenes, which causes rapid cell division. Approximately 50 percent of all people with myeloma have abnormally translocated chromosomes in their cancer cells.

Researchers have also determined that patients with plasma cell tumors have irregularities in other bone marrow cells known as dendritic cells. These irregularities may also trigger excess plasma cell growth. Dendritic cells release a hormone known as interleukin–6 (IL-6), which stimulates plasma cell growth. In excess, IL-6 seems to be an important factor in the development of plasma cell tumors.

In addition, researchers have identified a number of factors that may make a person more likely to develop multiple myeloma. These risk factors include:

• Age. A person’s age is the most significant risk factor for multiple myeloma. The average age at diagnosis is 68, and only 1 percent of cases are diagnosed in people under the age of 40.
  
  
• Gender. Men are more likely to develop multiple myeloma than women.
  
  
• Race. Multiple myeloma is approximately twice as common among African Americans as it is among white Americans.
  
  
• Exposure to radiation. People exposed to radioactivity from atomic blasts (such as those in Japan during World War II) and nuclear accidents have an increased risk of developing multiple myeloma.
  
  
• Family history. Although most patients have no affected relatives, multiple myeloma seems to be more common in some families.
  
  
• Working in a petroleum industry. Some research has suggested that workers in certain petroleum–related industries have an increased risk of developing the disease.
  
  
• Being overweight or obese. People who are overweight or obese have an increased risk of developing myeloma. 
  
  
• Having other plasma cell diseases. In some patients, multiple myeloma is preceded by another condition known as monoclonal gammopathy of undetermined significance (MGUS). Like multiple myeloma, MGUS is a disorder of excessive plasma cell growth. Over time, many people who have MGUS develop multiple myeloma or lymphoma.

Solitary plasmacytoma is another condition that increases a person’s risk of developing the disease. Unlike multiple myeloma, which involves numerous tumors, solitary plasmacytoma involves one tumor produced by uncontrollably growing plasma cells. Many patients with this disease eventually develop multiple myeloma as well.