Risk Factors and Causes

What are the risk factors for Waldenstrom macroglobulinemia?

A risk factor is anything that increases your chance of developing a disease. You are at higher risk for developing Waldenstrom macroglobulinemia (WM) if you:

  • Are male: WM is more common in men than women.
  • Are White: Caucasians are significantly more likely to develop WM than African Americans.
  • Are older: There are a few cases of WM occurring in younger people, but the chance of developing this disease increases as you age. WM is most often diagnosed in adults age 65 years and older.
  • Have a condition called IgM monoclonal gammopathy of undetermined significance (called IgM MGUS): This is a condition in which you have higher than normal levels of the antibody IgM – detected from blood tests – but no evidence of lymphoma.
  • Have a closely-related family member with WM or another type of lymphoma.
  • Have certain autoimmune diseases like Sjogren’s syndrome, or a viral illness such as hepatitis C. However, the relative importance of these factors has been difficult to determine.

How common is Waldenstrom macroglobulinemia?

WM is a rare disease. About 1,000 to 1,500 people are diagnosed with WM each year in the United States. WM accounts for approximately 1 to 2 percent of all blood (hematologic) cancers.

What causes Waldenstrom macroglobulinemia?

It’s not clear what causes WM. Experts think that changes – or mutations – in the genes of a B-lymphocyte cell is how the disease begins. These mutations tell the abnormal B-cell to continue to multiply uncontrollably. And because cancer cells don’t mature and then die as normal cells do, they accumulate and can overwhelm the production of healthy blood cells.

Recent research has identified two genetic mutations that may be found in people with WM.

  • MYD88 mutation: Most people with WM (about 90 percent) have an abnormal – or mutated – version of a gene known as MYD88.
  • CXCR4 mutations: Up to four out of 10 people with WM have changes to the gene known as CXCR4.

Researchers are studying what causes these genetic changes. They know they are not passed down from your parents. Most of the time, the mutations occur later in life which may explain why WM is usually diagnosed in older people. It’s likely these mutations do not cause WM by themselves, but in combination with other factors.