Association Between Nonsyndromic Congenital Heart Disease and Childhood Cancer in a Population‐Based, Retrospective Cohort of 11 Million Children
16 affiliations
- 1Division of Hematology–Oncology, Department of Pediatrics Baylor College of Medicine Houston TX USA
- 2Tilman J. Fertitta Family College of Medicine University of Houston Houston TX USA
- 3Present address: Department of Radiology University of New Mexico School of Medicine Albuquerque NM
- 4Division of Pediatric Cardiology, Department of Pediatrics Baylor College of Medicine and Texas Children's Hospital Houston TX USA
- 5Department of Genetic Medicine Johns Hopkins School of Medicine Baltimore MD USA
- 6Department of Epidemiology, Gillings School of Global Public Health University of North Carolina at Chapel Hill Chapel Hill NC USA
- 7Birth Defects Epidemiology and Surveillance Branch Texas Department of State Health Services Austin TX USA
- 8Department of Epidemiology, Fay W. Boozman College of Public Health and Winthrop P Rockefeller Cancer Institute University of Arkansas for Medical Sciences Little Rock AR USA
- 9Division for Family Health Data and Analytics Massachusetts Department of Public Health Boston MA USA
- 10Department of Biostatistics and Epidemiology, Hudson College of Public Health University of Oklahoma Health Campus Oklahoma City OK USA
- 11Department of Epidemiology, College of Public Health University of South Florida Tampa FL USA
- 12Chiles Center, College of Public Health University of South Florida Tampa FL USA
- 13Department of Epidemiology University of Texas MD Anderson Cancer Center Houston TX USA
- 14Department of Molecular and Human Genetics Baylor College of Medicine Houston TX USA
- 15Department of Pediatrics Emory University School of Medicine Atlanta GA USA
- 16Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta Atlanta GA USA
Abstract
Background: Epidemiologic studies have demonstrated associations between congenital heart disease (CHD) and childhood cancer. However, these assessments have not fully accounted for the pathogenetic and clinical heterogeneity of CHD, limiting their capacity to inform pathogenetic studies and the clinical management of children with CHD.
Methods: To achieve a more detailed understanding of cancer risk in children with nonsyndromic CHD, we evaluated 60 cardiac lesions in 7 categories in a cohort of 11 million children from Massachusetts, North Carolina, Oklahoma, and Texas. We used Cox proportional hazards regression to estimate the hazard ratios (HRs) and 95% CIs of cancer in children with each lesion relative to children without congenital anomalies when there were ≥3 co‐occurring cases.
Results: We identified 74 755 children with CHD and observed increased hazards for several malignancies. Notable associations included aortic arch obstruction–lymphoma (HR, 12.7 [95% CI, 4.9–31.0]); single‐ventricle disease–lymphoma (HR, 9.7 [95% CI, 3.8–24.4]); complex atrioventricular septal defect–leukemia (HR, 8.05 [95% CI, 2.8–23.0]); ventricular septal defect–hepatoblastoma (HR, 11.2 [95% CI, 5.9–21.1]); and conotruncal defects–neuroblastoma (HR, 6.4 [95% CI, 1.9–22.2]). The cumulative incidence of cancer was <1% for all CHD groups evaluated.
Conclusions: Cancer incidence in children with nonsyndromic CHD was generally low. However, we identified >5‐fold increases in the hazard of hepatoblastoma, neuroblastoma, leukemia, and lymphoma in children with certain lesions. Our findings may assist in generating hypotheses about the causes of cancer in children with CHD.
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BibTeX
@article{schraw2026association,
title = {{Association Between Nonsyndromic Congenital Heart Disease and Childhood Cancer in a Population‐Based, Retrospective Cohort of 11 Million Children}},
author = {Jeremy M. Schraw and Karin C. Mims and Sara B. Stephens and Sonja A. Rasmussen and Emily J. Mason and Tania A. Desrosiers and Charles J. Shumate and Wendy N. Nembhard and Mahsa M. Yazdy and Eirini Nestoridi and Amanda E. Janitz and Jean Paul Tanner and Russell S. Kirby and Jason L. Salemi and Chad D. Huff and Sharon E. Plon and Shaine A. Morris and Philip J. Lupo},
journal = {Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease},
year = {2026},
month = sep,
doi = {10.1161/jaha.125.050164},
url = {https://doi.org/10.1161/jaha.125.050164},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Association Between Nonsyndromic Congenital Heart Disease and Childhood Cancer in a Population‐Based, Retrospective Cohort of 11 Million Children
AU - Jeremy M. Schraw
AU - Karin C. Mims
AU - Sara B. Stephens
AU - Sonja A. Rasmussen
AU - Emily J. Mason
AU - Tania A. Desrosiers
AU - Charles J. Shumate
AU - Wendy N. Nembhard
AU - Mahsa M. Yazdy
AU - Eirini Nestoridi
AU - Amanda E. Janitz
AU - Jean Paul Tanner
AU - Russell S. Kirby
AU - Jason L. Salemi
AU - Chad D. Huff
AU - Sharon E. Plon
AU - Shaine A. Morris
AU - Philip J. Lupo
PY - 2026
DA - 2026/09/09
JO - Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
DO - 10.1161/jaha.125.050164
UR - https://doi.org/10.1161/jaha.125.050164
AB - Background: Epidemiologic studies have demonstrated associations between congenital heart disease (CHD) and childhood cancer. However, these assessments have not fully accounted for the pathogenetic and clinical heterogeneity of CHD, limiting their capacity to inform pathogenetic studies and the clinical management of children with CHD. Methods: To achieve a more detailed understanding of cancer risk in children with nonsyndromic CHD, we evaluated 60 cardiac lesions in 7 categories in a cohort of 11 million children from Massachusetts, North Carolina, Oklahoma, and Texas. We used Cox proportional hazards regression to estimate the hazard ratios (HRs) and 95% CIs of cancer in children with each lesion relative to children without congenital anomalies when there were ≥3 co‐occurring cases. Results: We identified 74 755 children with CHD and observed increased hazards for several malignancies. Notable associations included aortic arch obstruction–lymphoma (HR, 12.7 [95% CI, 4.9–31.0]); single‐ventricle disease–lymphoma (HR, 9.7 [95% CI, 3.8–24.4]); complex atrioventricular septal defect–leukemia (HR, 8.05 [95% CI, 2.8–23.0]); ventricular septal defect–hepatoblastoma (HR, 11.2 [95% CI, 5.9–21.1]); and conotruncal defects–neuroblastoma (HR, 6.4 [95% CI, 1.9–22.2]). The cumulative incidence of cancer was <1% for all CHD groups evaluated. Conclusions: Cancer incidence in children with nonsyndromic CHD was generally low. However, we identified >5‐fold increases in the hazard of hepatoblastoma, neuroblastoma, leukemia, and lymphoma in children with certain lesions. Our findings may assist in generating hypotheses about the causes of cancer in children with CHD.
SN - 2047-9980
ER -