Myeloma causes and risk factors

The exact cause of myeloma is not known. In most cases, there is no obvious reason why this rare blood cancer develops, although scientists have identified several environmental, demographic, and health-related risk factors that might contribute.

While many myeloma risk factors are beyond a person’s control, understanding the causes of myeloma can help individuals manage those that are modifiable. It can also aid in appropriate monitoring to ensure the disease is diagnosed and treated as early as possible.

Myeloma, often referred to as multiple myeloma, occurs when plasma cells — a group of antibody-producing immune cells — grow out of control in the bone marrow, the spongy tissue at the center of bones where blood cells are made. These myeloma cells, which don’t function the way normal plasma cells do, crowd out healthy blood cells and produce an abnormal antibody called M protein. This leads to a range of symptoms and complications.

As with other cancers, myeloma is believed to arise when plasma cells acquire genetic mutations that cause them to become cancerous and grow uncontrollably. There are a variety of risk factors that might drive that process.

While there is no definitive strategy for myeloma prevention, understanding its causes can help individuals manage modifiable risk factors and be aware of any need for closer monitoring.

Genetic factors

Myeloma occurs when plasma cells, the immune cells that normally produce antibodies to help fight off infections, grow out of control in bone marrow.

The condition arises due to genetic variations in plasma cells, but it is not always clear why these mutations develop. In most cases, the genetic changes linked to myeloma occur spontaneously during a person’s lifetime without a known trigger. Some people, however, may have a family history of myeloma and inherit genetic factors that increase their chances of developing the disease.

There is no single genetic cause of myeloma, and numerous genetic abnormalities have been implicated in this cancer.

Gene and chromosome changes

The cancer cells of most myeloma patients have one or more abnormalities in their chromosomes, the structures that carry DNA. These can include:

deletions, meaning a loss of all or part of a chromosome
duplications of part or all of a chromosome
translocations, or abnormal exchanges of genetic material between chromosomes

Mutations in specific cancer-related genes can also be observed, including in the following genes:

KRAS
NRAS
BRAF
MYC
TP53

Genetic mutations in myeloma often impair processes that help regulate how cells grow, divide, and survive, ultimately allowing plasma cells to grow out of control.

The role of family history

Because genetic abnormalities tied to myeloma are often acquired randomly throughout a person’s life, this cancer type is not considered a hereditary condition. Most people with the disease do not have a family history of it.

However, this blood cancer does occasionally run in families, and having a sibling or parent with myeloma is considered a risk factor. However, this could stem from a combination of shared environmental and genetic factors.

Environmental and lifestyle factors

There is no single environmental cause of myeloma, but environmental, lifestyle, and occupational risk factors have been linked to the disease. These include:

exposure to radiation
exposure to chemicals such as pesticides, fertilizers, herbicides, organic solvents, and combustion products
being overweight or obese

People who have occupational exposures to radiation or myeloma-associated chemicals may be at a particular risk. This specifically includes individuals who work in agricultural or industrial sectors and first responders in certain areas. Exactly how these environmental exposures may cause myeloma is not known, but they it’s believed they may contribute to cellular or DNA damage in plasma cells.

Obesity has been established as a modifiable risk factor for myeloma. It may have direct or indirect effects on cell growth, inflammation, and immune function, promoting an environment where cancer cells thrive.

Demographic factors

Various demographic factors may contribute to the risk of myeloma. Among them are:

age, with most people who develop myeloma being older than 65
sex, with men being slightly more likely to develop myeloma than women
race, with myeloma being twice as common and developing about five years earlier in Black people than in white people

Genetic changes that accumulate over a person’s lifetime may be one reason that myeloma occurs more often in older people. The exact reasons why the disease happens more in men and Black people have not been established, although underlying genetic factors could be involved.

Preexisting conditions and precursor disorders

People who have other diseases that affect plasma cells are at risk of progression to myeloma. The risk of developing myeloma may also be higher in people with certain conditions that affect immune system function.

Precursor plasma cell disorders

Active myeloma is almost always preceded by at least one of two precancerous conditions, known as precursor disorders. These are characterized by some elevation in plasma cells, but do not meet the diagnostic criteria for myeloma. However, not all people with these disorders will go on to develop myeloma.

Monoclonal gammopathy of unknown significance (MGUS) is an early precancerous condition in which plasma cells are slightly increased in the bone marrow. About 1% of people with MGUS develop myeloma each year.
Smoldering myeloma is an intermediate stage between MGUS and myeloma, characterized by 10%-60% plasma cells in the bone marrow. About 10% of people with this condition will develop myeloma each year.

Solitary plasmacytoma is a very rare blood cancer marked by a single mass of abnormal plasma cells in the bone, bone marrow, or soft tissues. It can also progress to myeloma. As many as 70% of people with plasmacytoma will develop myeloma, with the risk being higher when the plasmacytoma affects bone tissue.

Chronic immunosuppression and autoimmune diseases

People with weakened immune systems may also be at an increased risk of myeloma. This includes individuals:

with immune-suppressing diseases such as HIV/AIDS
taking immunosuppressive medications after an organ transplant
with the autoimmune disease pernicious anemia

Immune dysfunction may increase the risk of plasma cells becoming abnormal.

Emerging risk factors and ongoing research

Despite recent advances in the understanding of myeloma, exactly why plasma cells acquire disease-driving mutations remains not fully established. Scientists are still studying:

how specific genetic mutations affect cancer development and progression
new risk factors that could contribute to the disease
the mechanisms by which established risk factors contribute to the disease

More research into myeloma demographics may help scientists better understand who is at risk and allow them to develop early screening initiatives. Knowing more about the causes and mechanisms of myeloma will also enable researchers to develop more targeted therapies to treat the rare blood cancer in the future.

Rare Cancer News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Myeloma causes and risk factors