A review of: Hasle H, Clemmensen IH, Mikkelsen M 2000 Risks of leukemia and solid tumors in individuals with Down's syndrome. Lancet 355:165–169.

It is well established that the risk of leukemia is high in children with Down syndrome. A rare form of childhood leukemia, acute megakaryoblastic leukemia, is approximately 500 times more common in children with Down Syndrome than in normal children. In Down Syndrome that disease is found almost exclusively in children less than 4 years of age and frequently, if not always, in children who have recovered from a transient form of megakaryoblastic leukemia which is found in up to 10% of newborn infants with Down Syndrome (1). Acute lymphoblastic leukemia is also more frequent in children with Down Syndrome; however, the incidence is only about 6–10 times greater than in normal children. Does this predisposition to leukemia persist into adult life, and do other malignant disorders occur with high frequency in Down Syndrome?

Hasle et al., in a recent report, have provided some answers to these questions. They used the Danish Cytogenetics Registry to study the incidence of malignancy in 2814 cases of Down Syndrome registered from 1968 to 1994. As expected, the incidence of leukemia was high, 36 cases versus an expected 2 cases for a standardized incidence ratio (SIR) of 17.6. Also, as expected, the incidence was highest in young children. Of great interest, there were no cases of leukemia in adults older than 30 years (13,201 person-years at risk). The high risk of leukemia in Down Syndrome was limited to children.

Are malignant tumors, other than leukemia, more frequent in Down Syndrome? There have been reports of an increased incidence of germ cell tumors (2) and testicular tumors (3); however, the study of Hasle et al. could neither confirm nor reject those specific associations. What is of great interest is their observation that childhood malignancies were significantly less frequent than normal in children with Down Syndrome. They cite reports that children with Down Syndrome have a lower incidence than normal of solid tumors (4), neuroblastoma (5), and Wilms tumor. In the study of Hasle et al. of children with Down Syndrome (19497 person years at risk), there were no cases of neuroblastoma or Wilms Tumor. Overall, the incidence of solid tumors in patients with Down Syndrome (adults and children) was significantly lower than normal [expected = 47.8 cases; found = 24 cases SIR = 0.50 (95% confidence interval, 0.32–0.75)].

These remarkable and important findings indicate that the risk of leukemia in Down Syndrome is restricted to childhood, possibly reflecting an intrauterine origin of the disease. Furthermore, it appears that trisomy 21 offers “protection” against the development of solid tumors in children and adults. The nature of the susceptibility to leukemia and the resistance to solid tumors is unknown.