Rare Disease Report

The Link Between Gaucher Disease and Rare Cancers

JULY 21, 2015
Ruth J Hickman, MD
A review published in the American Journal of Hematology explores the potential reasons for the increased risk of non-Hodgkins B-cell lymphoma and myeloma found in Gaucher disease. These connections may lead to greater understanding of not only Gaucher disease, but potentially certain cancers as well. The paper’s first author is Timothy Cox, MD, Professor of Medicine at the University of Cambridge.1
Gaucher disease is the most prevalent lysosomal storage disorder in the world, affecting about 1 in 20,000 live births. The autosomal recessive condition is caused by mutations in the GBA gene, which provides instructions for making the enzyme β-glucocerebrosidase. The enzyme normally breaks down glucocerebroside into a sugar and a simpler fat molecule. With mutations in the GBA gene, the enzyme’s activity is reduced or eliminated, and glucocerebroside can build up to toxic levels within cells. Accumulation of these substances in tissue and organs can lead to a plethora of symptoms, including hepatosplenomegaly, anemia, thrombocytopenia, lung disease, bone abnormalities, and serious neurological damage, among others.1, 2
In recent years, the International Collaborative Gaucher Group (ICGG) Registry and other clinical surveys have made it easier to gather extensive clinical data about Gaucher disease, including comorbidities associated with the condition. The association between Gaucher disease and B cell proliferation and neoplasias and has been reported for several years. Though an increased risk has also been reported for other malignancies (e.g., hepatocellular cancer), the link between Gaucher and B cell neoplasias seems to be particularly strong. Patients with Gaucher disease have higher rates of polyclonal gammopathy, monoclonal gammopathy of undetermined significance, multiple myeloma, and B-cell non-Hodgkin’s lymphoma. One study in the ICGG Gaucher Registry found a relative risk of 5.9 for developing multiple myeloma.1

Many Theories, Few Answers

What is less clear is the reason for this association, though several theories have been suggested. It could be that build-up of a derivative of glucocerebroside has carcinogenic properties. Other researchers have suggested that one of the typical treatments for Gaucher disease may be responsible for this increased risk, though there is no evidence that the incidence of malignancies in patients treated for Gaucher disease has increased since the advent of enzyme replacement therapy.1
Another idea is that immune dysregulation in Gaucher disease might lead to the increased risk. The accumulated glucocerebroside seen in Gaucher disease may lead to a chronic stimulation of the immune system, causing lymphoproliferation. Specific cytokines released from macrophages in Gaucher disease (“Gaucher cells”) may promote chronic B cell stimulation and gammopathies. The cytokine IL-6 is elevated both in B cell neoplasias as well as in Gaucher disease, and it may potentially be one of the links between the conditions. Scientists are currently trying to tease apart these associations using a mouse strain that mimics Gaucher disease (and which also has a high rate of B cell tumors).1

Potentially, understanding why this rare disease increases the risk of these neoplasia might shed light on risk factors for certain cancers in people without Gaucher disease. Dr Cox and colleagues point out that work spent studying a rare disease like Gaucher disease can sometimes lead to breakthroughs in understanding more common conditions.  “Like other very rare inborn errors of metabolism, Gaucher disease is a paradigm case with numerous features that are generally applicable for clinical understanding in important conditions that are widespread in all populations.” 1


  1. Cox TM, Rosenbloom BE, Barker RA. Gaucher disease and comorbidities: B-cell malignancy and parkinsonism. Am J Hematol. 2015;90 Suppl 1:S25-8.
  2. Gaucher disease. Genetics Home Reference. http://ghr.nlm.nih.gov/condition/gaucher-disease. Reviewed September 2014. Accessed July 20, 2015.

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