There are numerous reports of cancers in Gaucher disease (GD) from mostly small single-center studies; however, precise risk estimates and cancer types involved have not been delineated. We conducted a study involving 2123 patients with GD type 1 (GD1) to assess the incidence of hematological malignancies, gammopathies, and solid tumors in an international observational study, the International Cooperative Gaucher Group Gaucher Registry (Clinicaltrials.gov: NCT00358943). Risk for cancer overall and for each type of malignancy was compared to the United States (US) population using the Surveillance, Epidemiology, and End Results database. Natural history of gammopathy was determined through assessing the progression from a diagnosis of monoclonal gammopathy of unknown significance (MGUS) to multiple myeloma (MM). Risk for hematological malignancies was more than four times higher than expected compared to the general population: non-Hodgkin lymphoma was approximately three times higher; MM was approximately nine times higher. Age-specific incidence rates of MGUS were unexpectedly high among younger patients. The 10-year cumulative incidence of MM after diagnosis of MGUS was 7.9%, comparable to the general population. Compared to the general US population, GD1 patients were at higher risk for solid malignancies of liver (2.9 times), kidney (2.8 times), melanoma (2.5 times), and breast (1.4 times). Colorectal, prostate, and lung cancer risks were lower than expected. These findings help advance care of patients with GD1 by supporting recommendations for individualized monitoring for malignancies and antecedents such as MGUS for MM and provoke important questions of the role of glucosylceramide and related sphingolipids in cancer biology.

中文翻译：

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国际戈谢集团戈谢登记处 2123 名患有 1 型戈谢病的成年人的癌症风险和丙种球蛋白病

有许多关于戈谢病 (GD) 癌症的报告，主要来自小型单中心研究；然而，精确的风险估计和所涉及的癌症类型尚未被描述。我们开展了一项涉及 2123 名 GD 1 型 (GD1) 患者的研究，以评估国际观察性研究国际合作戈谢组戈谢登记处 (Clinicaltrials.gov: NCT00358943) 中血液恶性肿瘤、丙种球蛋白病和实体瘤的发病率。使用监测、流行病学和最终结果数据库将总体癌症风险和每种类型的恶性肿瘤风险与美国 (US) 人口进行了比较。丙种球蛋白病的自然史是通过评估从意义不明的单克隆丙种球蛋白病 (MGUS) 诊断到多发性骨髓瘤 (MM) 的进展来确定的。与一般人群相比，血液系统恶性肿瘤的风险比预期高四倍多：非霍奇金淋巴瘤大约高三倍；MM 大约高出九倍。MGUS 的特定年龄发病率在年轻患者中出乎意料地高。MGUS 诊断后 MM 的 10 年累积发病率为 7.9%，与一般人群相当。与普通美国人群相比，GD1 患者患肝脏实体恶性肿瘤（2.9 倍）、肾脏（2.8 倍）、黑色素瘤（2.5 倍）和乳腺癌（1.4 倍）的风险更高。结直肠癌、前列腺癌和肺癌的风险低于预期。