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Deirdre A. Hill, PhD; Gloria Gridley, MS; Sven Cnattingius, MD; Lene Mellemkjaer, PhD; Martha Linet, MD; Hans-Olof Adami, MD; Jorgen H. Olsen, DMSc; Olof Nyren, MD; Joseph F. Fraumeni, Jr, MD

Arch Intern Med. 2003;163:705-711.

Background  Individuals with Down syndrome (DS) have a predisposition to leukemia and possibly other cancers and excess mortality from other conditions, but information on the magnitude of risk associated with specific cancers or causes of death is sparse.

Methods  Mortality experience and cancer incidence were evaluated in a combined cohort of 4872 individuals with a hospital discharge diagnosis of DS in Sweden (1965-1993) or Denmark (1977-1989) by linkage to national cancer and vital statistics registries. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were estimated by comparison with age, sex, and calendar-year expected values.

Results  Individuals with DS had an increased risk of incident acute lymphocytic (SIR, 24.2; 95% confidence interval [CI], 15.2-36.6; n = 22) and acute nonlymphocytic (SIR, 28.2; 95% CI, 15.7-48.3; n = 14) leukemias. Risks of testicular cancer (SIR, 3.7; 95% CI, 1.0-9.4; n = 4) and liver cancer (SIR, 6.0; 95% CI, 1.2-17.5; n = 3) were also elevated. Individuals with DS also experienced elevated mortality attributed to stomach cancer (SMR, 6.4; 95% CI, 1.7-16.4; n = 4), dementia and Alzheimer disease (SMR, 54.1; 95% CI, 27.9-94.4), epilepsy (SMR, 30.4; 95% CI, 13.9-57.7), ischemic heart disease (SMR, 3.9; 95% CI, 2.7-5.4), other heart disease (SMR, 16.5; 95% CI, 11.0-23.7), cerebrovascular disease (SMR, 6.0; 95% CI, 3.5-9.6), infectious diseases (SMR, 12.0; 95% 6.0-21.4), and congenital anomalies (SMR, 25.8; 95% CI, 21.0-31.4).

Conclusions  Individuals with DS have a substantially increased risk of mortality due to specific causes and may have an elevated risk of other incident cancers in addition to leukemia. These results provide clues regarding chromosome 21 gene involvement in diseases that complicate DS and are important for disease detection and care of affected individuals.

From the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md (Drs Hill, Linet, and Fraumeni and Ms Gridley); the Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden (Drs Cnattingius, Adami, and Nyren); and the Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark (Drs Mellemkjaer and Olsen).

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