Risks of leukaemia and solid tumours in individuals with Downʹs syndrome Original Research Article

Background Individuals with Downʹs 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 Downʹs syndrome from the Danish Cytogenetic Register, and linked the data to the Danish Cancer Registry. The number of person-years at risk was 48 453. 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 Downʹs 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 tumoursuppressor genes on chromosome 21.