Associations between Birth Defects with Neural Crest Cell Origins and Pediatric Embryonal Tumors

Citation

Wong, Eugene C.; Lupo, Philip J.; Desrosiers, Tania A.; Nichols, Hazel B.; Smith, Susan M.; Poole, Charles; Canfield, Mark A.; Shumate, Charles J.; Chambers, Tiffany M.; & Schraw, Jeremy M., et al. (2023). Associations between Birth Defects with Neural Crest Cell Origins and Pediatric Embryonal Tumors. Cancer, 129(22), 3595-3602. PMCID: PMC10615683

Abstract

BACKGROUND: There 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.
METHODS: With 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.
RESULTS: The 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.
CONCLUSIONS: Children 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.

URL

http://dx.doi.org/10.1002/cncr.34952

Reference Type

Journal Article

Year Published

2023

Journal Title

Cancer

Author(s)

Wong, Eugene C.
Lupo, Philip J.
Desrosiers, Tania A.
Nichols, Hazel B.
Smith, Susan M.
Poole, Charles
Canfield, Mark A.
Shumate, Charles J.
Chambers, Tiffany M.
Schraw, Jeremy M.
Nembhard, Wendy N.
Yazdy, Mahsa M.
Nestoridi, Eirini
Janitz, Amanda E.
Olshan, Andrew F.

Article Type

Regular

PMCID

PMC10615683

Data Set/Study

Genetic Overlap Between Anomalies and Cancer in Kids (GOBACK) Study

Continent/Country

United States

State

Nonspecific

Race/Ethnicity

Asian
Hispanic
Black
White
American Indian

ORCiD

Olshan - 0000-0001-9115-5128