Gaucher disease is an inherited disorder caused by a deficiency in the lysosomal hydrolase glucocerebrosidase. There is a wide spectrum of clinical presentations, with the most common features being hepatosplenomegaly, skeletal disease, and cytopenia. Gaucher disease has been classified into three broad phenotypes based upon the presence or absence of neurological involvement: Type 1 (nonneuronopathic), Type 2 (acute neuronopathic), and Type 3 (subacute neuronopathic). The two main treatment options include enzyme replacement therapy and substrate reduction therapy. Recently, discussion has escalated around the association of Gaucher disease and cancer, with conflicting reports as to whether Gaucher patients have an increased risk of malignancy. In this review, we present both the concept and controversy surrounding the association of Gaucher disease with cancer. 1. Introduction Gaucher disease is a panethnic autosomal recessive disorder characterized by a heterogeneous set of signs and symptoms caused by the defective hydrolysis of glucocerebroside. A deficiency in the enzyme glucocerebrosidase (glucosylceramidase, acid β-glucosidase) leads to the accumulation of glucocerebroside in the spleen, liver, and bone marrow. The resultant hepatosplenomegaly, haematological changes, and orthopaedic complications are the predominant symptoms [1]. Gaucher disease has been classified into three broad phenotypes. Type 1, the most common form, has no central nervous system involvement. Conversely, patients with Type 2 (acute neuronopathic disease) suffer from an aggressive form that leads to death perinatally or within the first few years of life. In Type 3 (subacute neuronopathic disease), patients show neurodegenerative symptoms but are able to survive through childhood to adulthood [2, 3]. The glucocerebrosidase gene is found on chromosome 1q21-22, consisting of 11 exons encoding a 497-amino-acid protein. A highly homologous pseudogene, located 16？kb downstream, complicates mutation analysis in this region. To date, nearly 300 mutations have been identified in Gaucher’s patients, including point mutations, deletions, insertions, splice site mutations, frame-shift mutations, and recombinant alleles [4–6]. Gaucher disease is the most common lysosomal storage disorder and the first to be successfully treated by enzyme replacement therapy [7]. In 1991, alglucerase (Ceredase, Genzyme Inc.), the placental derivative of glucocerebrosidase was FDA-approved. In 1994, the human recombinant-form imiglucerase (Cerezyme, Genzyme Inc.) received FDA approval. Alglucerase is
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