Are co-occurring structural birth defects associated with risk of acute lymphoblastic leukemia among children with Down syndrome

Background: Children with Down syndrome (DS) have a 15- to 20-fold increased risk of developing acute leukemia (ALL). While children with DS typically also present with multiple co-occurring major and minor structural birth defects, very little is known about whether the number and type of these co-occurring birth defects in children with DS are associated with risk of ALL. Methods: The Genetic Overlap Between Anomalies and Cancer in Kids (GOBACK) Study included linking data from population-based birth defects and cancer registries in Texas for the years 1999-2013. We performed a case-control analysis of ALL risk in participants diagnosed with DS. We evaluated the risk of ALL according to the presence of major birth defects in eight organ systems, as well as by the number of birth defects. Results: We identified 7,684 children with DS (controls) and 81 children with DS-ALL (cases) from among 5.7 million live births. There was a high burden of co-occurring birth defects in both the DS and DS-ALL groups, with 97% compared to 98% being diagnosed with at least one co-occurring birth defect (p = 0.39), respectively, and 68% compared to 71% being diagnosed with at least one major birth defect (p = 0.33). Similar to what has been reported among the general population of ALL patients, children with DS and ALL had a significantly higher mean birthweight (3088 vs 2891 g, p Conclusions: In this population-based assessment, we did not find strong evidence that co-occurring structural birth defects were related to ALL risk among children with DS. However, the small numbers of children with DS-ALL make it difficult to draw definitive conclusions. Citation Format: Jeremy M. Schraw, Tiffany M. Chambers, John P. Woodhouse, Peter H. Langlois, Mark A. Canfield, Angela E. Scheuerle, Michael E. Scheurer, Sharon E. Plon, Karen R. Rabin, Philip J. Lupo. Are co-occurring structural birth defects associated with risk of acute lymphoblastic leukemia among children with Down syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5054.