There is no definitely known cause of WM. As is the case with most cancers, there are probably multiple risk factors involved – some may be inherited predisposing genetic factors and some may be due to environmental or occupational exposures during one’s lifetime.
A risk factor is anything that increases the chances of developing a disease. The major risk factors that have been identified in WM include the following:
- Male sex – the incidence of WM is significantly greater in men than in women.
- Increasing age – the median age at diagnosis is approximately 65 years, although patients as young as 18 have been reported, and the annual incidence increases dramatically as age increases.
- White race – the incidence is higher in whites than in blacks, but reliable figures for other races are not available.
- IgM monoclonal gammopathy of undetermined significance (IgM MGUS) – refers to a condition in which the presence of a monoclonal IgM has been detected from blood tests, but there is no evidence of malignancy. In one long-term study of IgM MGUS, the incidence of progression to WM and other B-cell malignancies was 10% at 5 years, 18% at 10 years, and 24% at 15 years – a progression rate of approximately 1.5% each year.
Several reports suggest a link between WM and certain genetic, environmental, and viral factors. Studies report an element of familial susceptibility. Some evidence links the disease to a deletion in part of chromosome 6, although this abnormality is not present in all cases of WM. Environmental factors such as radiation exposure and occupational exposure to leather, rubber, paints, dyes, and solvents have also been implicated in some studies, as have certain autoimmune diseases and viruses such as hepatitis C. However, none of these factors has consistently been determined to increase risk.
The IWMF has been actively sponsoring research to discover genetic mutations in WM patients and determine their significance as risk factors for disease development and progression. Recent research has focused on a single mutation in a gene called MYD88. MYD88 initiates several downstream pathways in the cell that result in the expression of factors critical to the development and activation of B-cells. The mutation in this gene is called MYD88 L265P, and it is found in about 90% of WM patients. At this point, the significance of the mutation is not completely understood, although it appears to play an important role in continued proliferation of WM cells and may be a factor in the progression of IgM MGUS to WM. Other mutations found in a significant percentage of WM patients are also being studied. For a more detailed discussion about these new discoveries, see Future Directions.