Do patients with Gaucher disease have an increased risk of malignancy?

Several studies have investigated if patients with Gaucher disease have an increased risk of developing certain types of cancer. There is consistent evidence showing that patients with Gaucher disease are at particular risk for multiple myeloma and haematological malignancies.1-4

Data from the Gaucher Registry 2005

As of 30 September 2003, the International Gaucher Registry (sponsored by Sanofi Genzyme) contained information on almost 3000 patients with all types of Gaucher disease. In an analysis of registry data performed in 2005, the number of cancers identified among 2742 patients with Gaucher disease was compared with the rate of cancer expected in the US population of similar age and gender. Most patients were young or middle-aged adults (47% were aged 15‒44 years) at last known follow-up and most had Gaucher disease Type 1 (91.5%); 5.3% had Gaucher disease Type 3. The majority of patients (48.4%) were from the US, while 26.4% were from Europe and 5.8% were from the Middle East; 23.2% of patients were of Ashkenazi Jewish ethnicity. Of the 2742 patients studied, 126 (4.6%) had reported any type of cancer, and 98% of these patients had Gaucher disease Type 1.1

Of the 126 patients with Gaucher disease, the most commonly reported cancers are listed in Table 1.1 Compared with the lifetime probability of cancer expected in the US population, the observed number of cases of multiple myeloma in patients with Gaucher disease was higher than expected (10 vs 1.7), indicating that the relative risk for multiple myeloma was 5.9 (95% confidence interval [CI] 2.82‒10.82). However, the overall risk for cancer in patients with Gaucher disease was 0.79 (95% CI 0.67‒0.94), and there was no statistically significant increased risk for breast, colorectal, haematological, lung or prostate cancer. These data suggest that patients with Gaucher disease, at least those who are young or middle-aged, are not at a significantly higher risk of cancer, but that physicians should be aware of the increased specific risk of multiple myeloma in these patients.1

Table 1.
Lifetime probability of cancer by attained age in patients with Gaucher disease (N=2742). Reproduced with permission from Rosenbloom BE et al. Blood 2005; 105: 4569-4572.1


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In a Western European study from 2006, all medical files of patients with Gaucher disease Type 1 from the Academic Medical Centre in Amsterdam, The Netherlands, and the Heinrich Heine University Hospital, Düsseldorf, Germany, during the years 1993 to 2003 were reviewed. Of the 131 patients with mixed ancestry included in the study, 14 were diagnosed with a malignancy (Amsterdam, n=9/63; Düsseldorf, n=5/68), and there were five cancer-related deaths (Amsterdam, n=3; Düsseldorf, n=2). Haematological malignancy was identified in 5/14 patients (multiple myelomas, n=2; acute myeloid leukaemia, n=1; B-cell lymphoma, n=1; MALT lymphoma, n=1), which corresponds to an increased risk of haematological cancer of 12.7 (95% CI 2.6‒37.0) among patients with Gaucher disease compared with the general population, and an increased risk for cancer of 2.5 (95% CI 1.1‒4.7). Moreover, in the absence of pre-existing cirrhosis, the incidences of multiple myeloma and hepatocellular carcinoma were elevated, with standardised rate ratios of 51.1 and 141.3, respectively.2

Of the 403 patients included in a cross-sectional study, 54% were homozygous (N370S/N370S) and 46% were heterozygous (N370S/other) for the N370S mutation (c.1226A>G; p.Asp409Ser; see genetic inheritance of Gaucher disease). The majority of patients who were homozygous for N370S (c.1226A>G; p.Asp409Ser) displayed adult-onset disease with primarily a skeletal disease phenotype. For patients heterozygous for N370S (c.1226A>G; p.Asp409Ser), Gaucher disease was more likely to have an early onset, and visceral and haematological symptoms were significantly more present.3

The lifetime probability of first overall cancer by attained age in patients with Gaucher disease was significantly higher than expected (relative risk 1.80; 95% CI 1.32‒2.40; p<0.0001), as was the risk for other haematological malignancies (relative risk 3.45; 95% CI 1.49‒6.79; p<0.0001). Also, there was a high risk of multiple myeloma across the entire cohort (relative risk 25.0; 95% CI 9.17‒54.40; p<0.0001), especially for patients homozygous for the N370S (c.1226A>G; p.Asp409Ser) mutation.3

Results from a systematic review of the literature identified 365 studies, of which 80 reported concomitant Gaucher disease and malignancies and/or gammopathies (n=15 cohort/cross-sectional studies; n=65 case reports/series). Based on these studies, the authors concluded that, compared with the general population, patients with Gaucher disease may have an increased risk of cancer (pooled relative risk 1.70; 95% CI 1.27‒2.31), particularly for multiple myeloma (estimated risk 25.0‒51.1) and haematological malignancies (estimated risk 3.5‒12.7).4

C-ANPROM/INT//7566; Date of preparation: September 2020