What Causes Multiple Myeloma?

We know some risk factors for multiple myeloma, but it’s not always clear exactly what causes it. Here is what we do know about gene changes that can lead to multiple myeloma.

Multiple myeloma and MGUS progression

Scientists think multiple myeloma happens when a condition known as monoclonal gammopathy of undetermined significance (MGUS) progresses and becomes cancer.

About 1% of people with MGUS develop cancer such as multiple myeloma or lymphoma each year.

There are several types of gene changes (mutations) that cause MGUS to progress into multiple myeloma.

Gene changes (mutations) and cancer

Cancer is caused by changes in the genes inside our cells. This is true of all cancers, including multiple myeloma. In the next sections, we explain some of the specific gene changes that can lead to multiple myeloma.

But first, here is an overview of how gene changes cause cancer in general.

Cells, genes, and DNA

Cells are the basic building blocks of all living things, including our bodies. Genes are what control how cells function. DNA is the chemical in our cells that makes up those genes. Our DNA, which comes from both our parents, affects more than just how we look.

Different genes have different functions. When they are working properly, certain genes help control when our cells grow, divide to make new cells, or repair mistakes in DNA. They also cause cells to die when they’re supposed to.

Oncogenes, tumor suppressor genes, and DNA repair genes

If these genes aren’t working properly, it can cause cells to grow out of control. For example:

• Oncogenes: Changes in genes that normally help cells grow, divide, or stay alive can lead to these genes being more active than they should be, causing them to become oncogenes. These genes can result in cells growing out of control.
• Tumor suppressor genes: Genes that normally help keep cell division under control or cause cells to die at the right time are known as tumor suppressor genes. Changes that turn off these genes can result in cells growing out of control.
• DNA repair genes: Some genes normally help repair mistakes in a cell’s DNA. Changes that turn off these DNA repair genes can result in the buildup of DNA changes within a cell, which might lead to them growing out of control.

Any of these types of DNA changes might lead to cells growing out of control, which could lead to cancer. To learn more, see Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes.

Gene and chromosome changes and multiple myeloma

As mentioned above, scientists think multiple myeloma happens when a condition called MGUS progresses.

MGUS cells often have abnormal (unusual) chromosomes. Chromosomes are long strands of DNA inside each cell. Human cells normally have 23 pairs of chromosomes.

The most common chromosome changes in MGUS cells include:

• A translocation, in which part of one chromosome switches with part of another chromosome.
• A trisomy, in which there is an extra (third) copy of one of the chromosomes.

These types of changes can result in the cells having either overactive or extra copies of certain genes that help them grow.

Other types of genetic changes in the cells can then result in MGUS progressing to multiple myeloma.

Examples include:

• Activation of the MYC oncogene
• Deletion (loss) of the TP53 tumor suppressor gene
• Activation of oncogenes such as NRAS, KRAS, or BRAF

Changes in any of these genes (as well as some others) can cause the cells to grow out of control, which can lead to multiple myeloma.

What causes these gene changes?

We now know about many of the gene changes that cause multiple myeloma, but it’s not always clear what causes these changes. Some changes might be inherited from a parent. Other changes might be acquired, meaning they happen during a person’s life.

Some acquired gene changes might have outside causes. For example, exposure to radiation or certain chemicals might cause gene mutations that can lead to multiple myeloma.

But sometimes the gene changes in myeloma cells seem to happen for no clear reason. Many of these changes are probably just random events that sometimes happen inside a cell, without having an outside cause.

Gene changes inside cells can build up over a person’s lifetime, which might help explain why multiple myeloma largely affects older people.