Nonchromosomal Birth Defects and Risk of Childhood Acute Leukemia: An Assessment in 15 000 Leukemia Cases and 46 000 Controls From the Childhood Cancer and Leukemia International Consortium

Authors

Philip J Lupo
Tiffany M Chambers
Beth A Mueller
Jacqueline Clavel
John D Dockerty
David R Doody
Friederike Erdmann
Sameera Ezzat
Tommaso Filippini
Johnni Hansen
Julia E Heck
Claire Infante-Rivard
Alice Y Kang
Corrado Magnani
Carlotta Malagoli
Erin L Marcotte
Catherine Metayer
Helen D Bailey
Ana M Mora
Evangelia Ntzani
Eleni Th Petridou
Maria S Pombo-de-Oliveira
Wafaa M Rashed
Eve Roman
Joachim Schüz
Catharina Wesseling
Logan G Spector
Michael E Scheurer

Publication Date

2-1-2024

Journal

International Journal of Cancer

DOI

10.1002/ijc.34720

PMID

37694915

PMCID

PMC11034994

PubMedCentral® Posted Date

4-22-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Child, Humans, Infant, Risk Factors, Leukemia, Myeloid, Acute, Birth Weight, Logistic Models, Case-Control Studies, Surveys and Questionnaires, Epidemiology, childhood leukemia, birth defects, acute lymphoblastic leukemia, acute myeloid leukemia

Abstract

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.