Multiple myeloma (MM) is a type of blood cancer affecting the plasma cells. Although doctors do not know what causes MM, a person’s genetics may contribute to their risk of developing it.

Multiple myeloma (MM) starts in the plasma cells, which are a type of white blood cell. In healthy individuals, white blood cells protect the body from germs and possible infections.

However, in people with MM, the white blood cells do not function properly. Instead of producing essential antibodies, they produce abnormal ones.

Doctors are not sure what causes MM. However, they know genetics play a role. All cancer is inherently genetic, and all cancer cells have gene mutations that cause cancerous growth. Although MM usually occurs when plasma cells have mutations, people with a family history of MM may be at higher risk for developing the condition.

Other factors that increase a person’s risk are age, race, and sex.

Read more to learn about the genetic factors of MM, other risk factors, and triggers for the disease.

A person holding the hands of a family member with multiple myeloma.Share on Pinterest
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MM, like all cancers, has a genetic component.

However, it may also have a hereditary component, which means it may run in families. People are at higher risk for developing it if they have a first-degree relative (a parent or sibling) with myeloma.

However, many people with MM do not have a relative with the condition.

One 2016 analysis of multiple studies looked at the MM risk of people with a first-degree relative who had lymphohematopoietic cancers. This included lymphomas, leukemia, and MM.

People with a family history of these conditions were 1.29 times more likely to develop MM. The study showed that a person’s risk increased further if they had multiple relatives with these cancers.

According to the International Myeloma Foundation, approximately 5–7% of MM cases occur in people who have a close relative previously diagnosed with myeloma or monoclonal gammopathy of undetermined significance (MGUS). MGUS is a noncancerous condition that can be a precursor to MM.

Researchers are still learning how genetics affect MM.

Studies show that genetics contribute to the disease’s progression. Over time, genetic “hits” affect a person’s plasma cells, causing the condition to worsen.

The genetic factors causing these hits can be traced back to a person’s chromosomes. Most people have 23 pairs of chromosomes — 46 in total — that contain their genetic material.

Research links certain chromosomes to MM.

Sometimes, these chromosomes incur damage. One way this happens is through chromosomal translocation, which is when part of one chromosome breaks off and attaches to another. About 50–70% of people with myeloma have chromosomal translocations. Over 90% of these translocations involve chromosome 14.

Identifying these translocations helps doctors understand a person’s disease.

Various genes may contribute to a person’s risk of developing MM. They include:

DIS3

RNA is similar to DNA, but instead of having two strands, it has one. It holds genetic code and can carry viruses.

The DIS3 gene encodes an RNA exonuclease, which is an enzyme that removes pieces of the RNA code. They act as “proofreaders” for the genetic code.

This can cause a loss of function.

Research has shown DIS3 is mutated in about 10% of MM cases.

FAM46C

The FAM46C gene supports ribosomal proteins. These are responsible for carrying out protein synthesis, which is when proteins are assembled.

Proteins are essential for many bodily functions, including fighting infections, carrying out chemical reactions, and transmitting signals between cells.

If genes involved in creating proteins, like the FAM46C gene, become damaged or changed, it can affect every tissue in the body.

FAM46C mutations are common in people with MM.

BRAF

BRAF mutations affect a specific protein responsible for regulating cell growth. This means people with this gene mutation have no cell growth regulation, and cells can grow out of control.

Although this mutation is common, people with MM often benefit from medications called BRAF inhibitors.

These drugs stop the uncontrolled cell growth and can slow the progression of MM in some people.

Other gene mutations

Many genes contribute to a person’s likelihood of developing MM. Other gene mutations include:

  • EGR1: This gene mutation may be involved in drug resistant myeloma cells.
  • KRAS: This commonly mutated gene is present in 36% of MM cases.
  • NRAS: This common mutation is present in 20% of cases and more common in relapses.
  • TP53: About 26% of people with MM have this mutation.
  • IRF4: This controls how plasma cells develop.
  • PRDM1: This gene affects how plasma cells differentiate cell types.
  • SP140: This gene is found in plasma cells.
  • XBP1: Mutations of this gene may affect the cell’s sensitivity to proteasome inhibitors, an important type of medication for treatment.

Risk factors are anything that increases a person’s risk of developing a disease.

In the case of MM, some common risk factors include age, gender, race, weight, and other plasma cell diseases.

Age

As people get older, their risk of developing MM goes up. However, this is not unique to MM. The risk of developing most cancers increases with age.

Most people diagnosed with MM are between the ages of 66 and 70. It is very rare in younger individuals, and just 0.02-0.3% of cases affect people under 30.

Gender

Men are at a slightly higher risk of developing MM compared to women.

Race

MM is about twice as common in African Americans. There is increasing evidence that people of African American descent are genetically predisposed to have a higher risk of developing MM.

Some research suggests MM symptoms start earlier in Black people. They also have a higher mortality rate.

Obesity

Having obesity or overweight may increase someone’s risk of developing MM.

Having other plasma cell diseases

Plasma cell diseases include monoclonal gammopathy of undetermined significance (MGUS) and solitary plasmacytoma.

If an individual has one of these conditions, they have a higher risk of developing MM. People with MGUS have a 1% increase in their likelihood of developing MM per year.

Radiation exposure

People exposed to X-rays or other forms of ionizing radiation may have a higher risk of developing MM.

Experts have linked various toxic chemicals to MM. Chemical triggers include:

  • benzene
  • solvents
  • agricultural chemicals
  • fuels
  • engine exhausts
  • cleaning products
  • dioxins

Several viruses are also potential triggers of MM. These include:

MM is a rare cancer affecting a person’s plasma cells. Research suggests genetics may contribute to a person’s likelihood of developing the disease.

People with a close family member with lymphomas, leukemia, or myeloma are 1.29 times more likely to get MM. This may be the result of several gene mutations. Some gene mutations trigger the disease, make it spread faster, and impact the effectiveness of treatment.

Other risk factors for MM include age, gender, race, obesity, and having other plasma cell diseases. Toxic chemicals and some viruses may also trigger MM.