Chapter Five - Cancer among Persons with Down Syndrome

Abstract

The overall incidence of cancer in children and adults with Down syndrome (DS) appears the same as in the general population. The distribution of tumor types, however, is markedly different. The risk for leukemia in children with DS is 10–20-fold higher than in children without DS. In contrast, solid tumors both of childhood and adult age are markedly less frequent in people with DS. Leukemia is the predominant type of cancer in DS. In children with DS under the age of 5 years, acute myeloid leukemia (AML) is approximately 150-fold and acute lymphoblastic leukemia (ALL) approximately 40-fold more common than in the general pediatric population. The leukemic cells of AML in DS commonly have a platelet precursor phenotype and harbor somatic mutations of the hematopoietic transcription factor GATA1. AML cells of children with DS show increased sensitivity to some chemotherapeutic agents such as cytarabine. Event-free survival (EFS) rates after treatment for AML in DS range between 70 and 90% and are significantly higher than for non-DS children with AML. Newborns with DS in 10% of cases develop a transient leukemia which typically resolves after the first months of life without treatment. Approximately 20% of infants with transient leukemia, however, go on to develop AML later in life. ALL in children with DS is considered the same disease as in the general pediatric population. After treatment outcomes in the past lagged behind that for children without DS, currently the success rate of treatment for ALL in DS is now considered comparable to that for non-DS ALL. The risk for severe adverse events during treatment, specifically life-threatening infections, is increased in children with DS and ALL. Increased expression of the gene CRLF2 (cytokine receptor-like factor 2) and activating mutations of JAK2 have been recently identified as more frequently associated with ALL in DS. The incidence of most solid tumors of childhood and adult age has been found to be significantly lower in individuals with DS. Although the mechanisms underlying both the increased frequency of leukemia and the decreased incidence of solid tumors in DS remain to be determined, intriguing hypotheses have been proposed.