Structural birth defects and leukemia risk in children with Down syndrome

Area of Science:

• Pediatric Oncology
• Clinical Genetics
• Cancer Epidemiology

Background:

• Birth defects increase cancer risk in children generally.
• The relationship between birth defects and leukemia risk in children with Down syndrome (DS) is not well understood.

Purpose of the Study:

• To investigate the impact of major birth defects on the risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in children with Down syndrome.

Main Methods:

• Utilized data from 26,660 children with DS from the Genetic Overlap Between Anomalies and Cancer in Kids Registry Linkage Study.
• Assessed cumulative incidence of ALL and AML in children with and without co-occurring major birth defects.
• Calculated adjusted hazard ratios (aHR) for leukemia risk based on the presence and type of birth defects.

Main Results:

• 71.9% of children with DS had at least one major birth defect, primarily cardiac, musculoskeletal, or gastrointestinal.
• Overall leukemia incidence was comparable between children with and without co-occurring major birth defects (aHR for ALL: 1.12, aHR for AML: 1.09).
• Anophthalmia/microphthalmia was linked to increased ALL risk (aHR: 2.83), and tetralogy of Fallot to increased AML risk (aHR: 2.40).

Conclusions:

• Major birth defects do not significantly elevate overall leukemia risk in children with Down syndrome.
• Certain specific birth defects, anophthalmia/microphthalmia and tetralogy of Fallot, are associated with specific leukemia types in this population.
• Unlike the general pediatric population, birth defects in children with DS do not appear to be a strong determinant of leukemia risk.