Affiliation:
1. Department of Epidemiology Gillings School of Global Public Health The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
2. Section of Hematology‐Oncology Department of Pediatrics Baylor College of Medicine Houston Texas USA
3. Department of Nutrition Gillings School of Global Public Health The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA
4. Birth Defects Epidemiology and Surveillance Branch Texas Department of State Health Services Austin Texas USA
5. Department of Epidemiology Fay W. Boozman College of Public Health University of Arkansas for Medical Sciences and Arkansas Center for Birth Defects Research and Prevention Little Rock Arkansas USA
6. Massachusetts Center for Birth Defects Research and Prevention Massachusetts Department of Public Health Boston Massachusetts USA
7. Department of Biostatistics and Epidemiology Hudson College of Public Health University of Oklahoma Health Sciences Center Oklahoma City Oklahoma USA
Abstract
AbstractBackgroundThere are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.MethodsWith the use of a multistate, registry‐linkage cohort study, BDNCO–embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education.ResultsThe risk of embryonal tumors among those with BDNCOs was 0.09% (co‐occurring n = 105) compared to 0.03% (95% CI, 0.03%–0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5–5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3–22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3–4.2) and nephroblastoma (2.9; 95% CI, 1.9–4.4) were elevated. There was no notable HRM by the aforementioned factors.ConclusionsChildren with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions.
Funder
Defense Human Resources Activity