Is Multiple Myeloma Genetic? What there is to know

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

Multiple myeloma (MM) starts in 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, white blood cells do not work properly. Instead of producing essential antibodies, they produce abnormal ones.

Doctors don’t know what causes MM. However, they know that genetics play a role. All cancer is inherently genetic, and all cancer cells have genetic 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 of developing the disease.

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

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

MM, like all cancers, has a genetic component.

However, it can also have a hereditary component, which means it can run in families. People are more at risk of 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 disease.

A 2016 analysis of several studies examined the risk of MM in people with a first-degree relative with 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 found that a person’s risk increased more if they had more than one parent with these cancers.

According to the International Myeloma Foundation, about 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 non-cancerous disease that can be a precursor to MM.

Researchers are still learning how genetics affect MM.

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

The genetic factors behind these hits can be traced 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 are damaged. This happens in particular through chromosomal translocation, that is, when part of a chromosome breaks and attaches to another. On 50-70% of people with myeloma have chromosomal translocations. More than 90% of these translocations concern chromosome 14.

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

Various genes may contribute to the risk of developing MM. They understand:

DIS3

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

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

This can lead to loss of function.

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

FAM46C

The FAM46C gene supports ribosomal proteins. These are responsible for protein synthesis, that is, when proteins are put together.

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

If genes involved in the creation of proteins, such as the FAM46C gene, are damaged or changed, it can affect all tissues 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 that people with this genetic mutation have no regulation of cell growth, and cells can grow out of control.

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

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

Other genetic mutations

There are many genes that contribute to the likelihood that a person will develop MM. Other genetic mutations include:

  • EGR1: This genetic mutation could be involved in drug resistant myeloma cells.
  • KRAS: This commonly mutated gene is present in 36% cases of MM.
  • NRAS: This common mutation is present in 20% cases and more common in relapses.
  • TP53: On 26% of people with MM have this mutation.
  • IRF4: This controls the development of plasma cells.
  • PRDM1: This gene affects the way plasma cells differentiate between cell types.
  • SP140: This gene is found in plasma cells.
  • XBP1: Mutations in this gene can affect the cell’s sensitivity to proteasome inhibitors, an important type of drug 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, sex, race, weight, and other diseases of the plasma cells.

Age

As people get older, their risk of developing MM increases. 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 people, and 0.02-0.3% of cases concern people under the age of 30.

Kind

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

Race

MM is on twice also common among African Americans. It is increasingly evident that people of African American descent are genetically predisposed have a higher risk of developing MM.

Some research suggests that symptoms of MM start earlier in black people. They also have a higher death rate.

Obesity

Being obese or overweight Can increase someone’s risk of developing MM.

Have other plasma cell diseases

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

If a person has any 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 to develop MM.

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

  • benzene
  • solvents
  • agricultural chemicals
  • fuels
  • engine exhausts
  • Cleaners
  • dioxins

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

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

People with a close family member who have lymphoma, leukemia or myeloma are 1.29 times more likely to get MM. This can be the result of several genetic mutations. Certain genetic mutations trigger the disease, accelerate its spread and impact the effectiveness of treatment.

Other risk factors for MM include age, gender, race, obesity, and other diseases of the plasma cells. Toxic chemicals and some viruses can also trigger MM.


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