Causes, Risk Factors, and Prevention of Waldenstrom Macroglobulinemia

The cause of most Waldenstrom macroglobulinemia (WM) is not completely understood.

Researchers have found a few risk factors that make a person more likely to develop WM. But having a risk factor doesn’t mean you will get the disease. Most people with these risk factors don’t develop WM.

What causes Waldenstrom macroglobulinemia?

Researchers have made great progress in understanding how certain gene mutations (changes) can cause normal cells to become cancerous. For example, some genes contain instructions for controlling when our cells grow and divide.

Mutations in these genes can lead to cancer growth.

We still don’t know exactly what causes Waldenstrom macroglobulinemia (WM), but researchers are beginning to understand how certain gene changes may play a role.

Gene changes found in WM cells

Certain gene changes in normal B cells can alter the way the gene works. When this happens, it can promote cancer growth and lead to a person developing WM.

Scientists don’t yet know the exact cause of gene changes that lead to WM, but they do know that certain gene changes are seen more commonly in WM cells. When doctors know what gene changes are present in WM, they can use this information to help figure out the best treatment and predict how your cancer will respond.

In the case of WM, 4 main gene changes have been seen.

Are these gene changes inherited or acquired?

The changes found in WM cells are usually acquired, meaning they happen after you are born. They are not usually inherited (passed on from a parent).

Some of these acquired changes may have outside causes, but often they happen for no apparent reason. They seem to happen more often as we age, which might help explain why WM usually occurs in older people.

Risk factors for Waldenstrom macroglobulinemia

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like your age or family history, cannot be changed.

Although Waldenstrom macroglobulinemia (WM) is rare, it is most common in:

• Men
• White people
• People over the age of 50

Researchers have found a few other risk factors that make a person more likely to develop WM.

Genetic risk factors

Most WM is caused by acquired gene changes after birth, but some people with a family history of WM may be at an increased risk.

About 1 in 5 people with WM have a close relative with WM or with a related B-cell disease, such as monoclonal gammopathy of undetermined significance (MGUS), or certain types of lymphoma or leukemia.

Environmental risk factors

Studies of environmental exposures suggest that exposure to farming, pesticides, and wood dust may increase the risk of developing WM. More studies are needed to understand if exposure to chemicals or other things in the environment plays a role in WM.

Other risk factors

Monoclonal gammopathy of undetermined significance (MGUS)

Monoclonal gammopathy of undetermined significance (MGUS) is a condition related to multiple myeloma and WM. In MGUS, abnormal plasma cells make many copies of the same IgM antibody (called a monoclonal protein). These plasma cells make up less than 10% of the bone marrow and they do not form an actual tumor or mass.

MGUS itself does not cause health problems, but each year about 1-2% of people with MGUS go on to develop a related cancer like WM, multiple myeloma, lymphoma, or another serious health problem like amyloidosis.

Chronic hepatitis C infection

Some studies have found that people with chronic hepatitis C infection might be more likely to develop WM than people without the virus. But not all studies have found this link.

Certain autoimmune diseases

Some research has suggested that people with certain types of autoimmune disease, such as autoimmune anemias and Sjögren (Sjogren) syndrome, might be at higher risk for WM.

Can Waldenstrom macroglobulinemia be prevented?

Most of the risk factors for Waldenstrom macroglobulinemia (such as older age or MGUS) cannot be changed or controlled, so there is no way to prevent cancers related to these risk factors.

Some research suggests that people with hepatitis C might be more likely to develop WM. There is currently no vaccine to prevent hepatitis C, but avoiding activities like injection drug use or unprotected sex with many partners can reduce the risk of getting the virus.

Researchers don’t know if treating conditions associated with WM, like hepatitis C or autoimmune diseases, changes the risk for developing WM.