Risks of leukaemia and solid tumours in individuals with Down's syndrome.

BACKGROUND: Individuals with Down's syndrome have a greater risk of leukaemia than the general population, but reliable estimates of the age-specific risk are lacking and little is known about the risk of solid tumours.

METHODS: We identified 2814 individuals with Down's syndrome from the Danish Cytogenetic Register, and linked the data to the Danish Cancer Registry. The number of person-years at risk was 48453. Standardised incidence ratio (SIR) and 95% CI were calculated of the basis of cancer rates specific for age and sex in the general population.

FINDINGS: 60 cases of cancer were found, with 49.8 expected (SIR 1.20 [95% CI 0.92-1.55]). Leukaemia constituted 60% of cases of malignant disease overall and 97% of cases in children. The SIR for leukaemia varied with age, being 56 (38-81) at age 0-4 years and 10 (4-20) at 5-29 years. No cases of leukaemia were seen after the age of 29 years. The SIR for acute myeloid leukaemia was 3.8 (1.7-8.4) times higher than that for acute lymphoblastic leukaemia in children aged 0-4 years. The cumulative risk for leukaemia by the age of 5 years was 2.1% and that by 30 years was 2.7%. Only 24 solid tumours were seen, with 47.8 expected (0.50 [0.32-0.75]). No cases of breast cancer were found, with 7.3 expected (p=0.0007). Higher than expected numbers of testicular cancers, ovarian cancers, and retinoblastomas were seen but were not significant. INTREPRETATION: The occurrence of cancer in Down's syndrome is unique with a high risk of leukaemia in children and a decreased risk of solid tumours in all age-groups. The distinctive pattern of malignant diseases may provide clues in the search for leukaemogenic genes and tumour-suppressor genes on chromosome 21.