Causes and Risk Factors of Multiple Myeloma

What causes this rare cancer?

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Multiple myeloma (sometimes referred to as myeloma) is a rare type of blood cancer that involves the abnormal growth of plasma cells—a type of white blood cell—that accumulate uncontrollably in the bone marrow. The immune system is impacted due to the inefficiency of the plasma cells to produce healthy antibodies, which fight infection. The overgrowth of plasma cells crowds other blood cells, reducing the number of healthy red and white blood cells.

This often results in conditions such as frequent infections, anemia, low platelet count (blood clotting cell count), and more. The myeloma cells can also result in painful bone tumors and destruction of bone tissue that leads to a high risk of bones that are easily fractured. In the late stage of the disease, the organs may be affected due to myeloma cells producing abnormal antibodies—called M proteins—that build up in the body, causing damage to the kidneys.

Common Causes

The exact cause of multiple myeloma is unknown. However, what researchers do know about multiple myeloma is the fact that the condition starts with the abnormal growth of a plasma cell in the bone marrow. Next, the abnormal cell begins to multiply rapidly. 

The symptoms occur due to the abnormal duplication of the plasma cells in the bone marrow, but no one knows exactly what causes the plasma cells to begin this abnormal growth pattern. 

Research scientists hypothesize that there are probably several causes that contribute.

Genetic Abnormalities

These are changes or mistakes in the DNA. The DNA contains the code of instructions that tell each cell how to perform, grow, divide, and when to stop multiplying. These mistakes are called “mutations” and they may cause plasma cells to become cancerous. The DNA is packaged into chromosomes in the cells. 

According to the American Cancer Society, “Myeloma cells also show abnormalities in their chromosomes. In about half of all people with myeloma, part of one chromosome has switched with part of another chromosome in the myeloma cells.” When this occurs in an area next to a gene that is responsible for how the plasma cell grows and divides, it can result in cancerous plasma cells.

Bone Marrow Abnormalities

Some of the bone marrow abnormalities involve dendritic cells—they may cause plasma cells to grow and develop abnormally, which may contribute to plasma cell tumors.

Environmental Factors

Environmental factors, such as exposure to certain chemicals or radiation, have been implicated as a contributing factor in the cause of multiple myeloma. 

It’s important to note that most people who are diagnosed with multiple myeloma and who are screened for risk factors end up having no known risk factors other than age.

Genetics

Although it is known that cancer is caused by changes called “genetic mutations” to the DNA inside of the cells, the underlying reason these changes occur is not completely clear to researchers. 

Most cancers, including multiple myeloma, are thought to occur due to mutations of genes that occur after birth, influenced by factors such as carcinogens (cancer-causing chemicals). The body has a normal way of fixing mistakes that occur when a cell grows and gene mutations occur, however, occasionally, the mistake is overlooked—this could cause the cell to become cancerous. 

Another common genetic mistake that is very common in those with myeloma is a missing piece of chromosome 13, or the entire chromosome missing in many cases. In fact, one study involving 1,500 multiple myeloma patients was reported by the American Society of Clinical Oncology (ASCO). According to the lead study author, Guido J. Tricot, MD, PhD., "Chromosomal studies are the most important prognostic factor in the treatment of myeloma."

He went on to say that "Chromosome 13 deletion and hypodiploidy [having slightly less than the normal number of chromosomes] is associated with poor prognosis, but too many institutes are failing to do these studies which can predict outcome and help customize treatment."

Approximately 50 percent of the people diagnosed with multiple myeloma have a deletion of chromosome 13.  

Although it is not clearly understood why the chromosome deletion occurs in those with myeloma, these patients are known to have a marked reduction in survival rates. They also have a higher incidence of resistance to traditional myeloma treatment regimes.

Lifestyle Risk Factors

A risk factor is something that can increase the chance of someone getting a disease, such as cancer. Each type of cancer has its own risk factors. For example, smoking causes an increased risk of getting lung cancer, and prolonged exposure to the sun proposes an increased risk of skin cancer.

However, risk factors do not necessarily indicate that a person will get a specific type of cancer. People with no risk factors at all often get a disease, including cancer. Those having one (or even several) risk factors may never get a disease. Generally, there are two types of risk factors, including non-modifiable and modifiable risk factors.

Non-Modifiable Risk Factors

Non-modifiable risk factors are those that cannot be changed. For multiple myeloma, these include a number of factors.

  • Age. Most commonly, the disease occurs in those over 60 years old, and only a small percentage (2 percent) of the those who have been diagnosed are under 40. The average age to be diagnosed with myeloma is 70.
  • Sex. Men are slightly more prone to getting multiple myeloma than women.
  • Race. Myeloma is said to be more prevalent in the Middle East, North Africa, and the Mediterranean region. Although the underlying reason is unknown, the prevalence of the disease occurs twice as often in African Americans than in Caucasians. 
  • Family history. Although some sources report a strong familial link to myeloma, a 2018 report by the American Society of Clinical Oncology (ASCO) stated, "There appears to be a slight increase in the incidence of the disease in first-degree relatives (parents or siblings) of people with multiple myeloma.”

However, the ASCO also stated that "Mutations or changes in plasma cells are acquired, not inherited, so having a relative with the disease usually does not mean another family member is at higher risk for developing it."

Modifiable Risk Factors

Modifiable risk factors are those that can be changed. These usually include lifestyle factors, such as diet and exercise. For multiple myeloma, however, the primary modifiable risk factors involve exposure to environmental substances (usually related to a person’s occupation).

Exposure to Chemicals or Radiation

Exposure to chemicals such as those in asbestos and pesticides, as well as exposure to benzene—a substance present in rubber manufacturing—may pose an increased risk of developing myeloma. Exposure to certain types of plastics, heavy metal dust, hair dyes, herbicides (including Agent Orange), and pesticides may also increase the risk of getting myeloma. 

Radiation exposure has been found to have a very strong link to myeloma as well. For example, those who were exposed to radiation from the atom bomb, during World War II (in Nagasaki and Hiroshima) were found to have a significantly higher incidence of multiple myeloma compared to the general population.

Occupational Exposure

This is linked to the exposure to specific chemicals and includes people working in the leather, cosmetology, rubber, and petroleum fields. Other occupational types of exposure that may increase the risk of myeloma include working with wood products (those who make furniture, paper makers, or carpenters). Farmers and professional firefighters are also thought to have an increased risk of getting myeloma.

Obesity or Being Overweight

Obesity or being overweight is also linked with a higher risk of most types of cancer—this includes multiple myeloma. Both obesity and being overweight are considered modifiable risk factors for multiple myeloma that directly pertain to a person's lifestyle.

Other Risk Factors

Personal Health History

Those who have had prior plasma cell conditions (such as plasmacytoma of the bone or monoclonal gammopathy) are at greater risk of developing myeloma than those who have not had these conditions.  

Monoclonal Gammopathy (MGUS)

Just about every case of myeloma begins as what Mayo Clinic describes as “a relatively benign condition called monoclonal gammopathy of undetermined significance (MGUS).” Mayo Clinic goes on to explain that “In the United States, about 3 percent of people older than age 50 have MGUS. Each year, about 1 percent of people with MGUS develop multiple myeloma, or a related cancer.”

The cause of MGUS is unknown. It is a condition that involves the presence of M protein, like myeloma, but the level of M protein is lower in MGUS. Also, there is not any damage to the body in MGUS (such as organ or bone damage).

A Word From VeryWell

We realize that for those who are diagnosed with multiple myeloma, not knowing the exact cause of an illness—particularly one that is as severe as myeloma—can be very frustrating. Although experts are unsure of the exact cause of cancer, medical research continues to reveal new and more effective treatment modalities that are aimed at improving the survival rates. As the incidence of myeloma continues to rise, so do the efforts to find a cure. More efforts are aimed at slowing down the progression of the disease, which would give patients more years of symptom-free life.

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