Association Between Nonsyndromic Congenital Heart Disease and Childhood Cancer in a Population-Based, Retrospective Cohort of 11 Million Children.

Aortic arch obstruction was associated with a markedly elevated hazard of lymphoma in children with nonsyndromic congenital heart disease.

• Hazard ratio for aortic arch obstruction-lymphoma: HR 12.7 (95% CI, 4.9–31.0)
• This was one of the largest effect sizes observed in the study
• Analysis was restricted to lesion-cancer combinations with ≥3 co-occurring cases
• Cox proportional hazards regression was used with children without congenital anomalies as the reference group

Single-ventricle disease was associated with a nearly 10-fold increased hazard of lymphoma.

• HR for single-ventricle disease-lymphoma: 9.7 (95% CI, 3.8–24.4)
• Single-ventricle disease was one of 7 categories of cardiac lesions evaluated
• 60 distinct cardiac lesions were evaluated across the full study
• The cohort included 74,755 children with CHD

Complex atrioventricular septal defect was associated with more than 8-fold increased hazard of leukemia.

• HR for complex atrioventricular septal defect-leukemia: 8.05 (95% CI, 2.8–23.0)
• This association was among several notable leukemia findings in the study
• The study evaluated associations in a population-based, retrospective cohort of approximately 11 million children
• Data were drawn from Massachusetts, North Carolina, Oklahoma, and Texas

Ventricular septal defect was associated with an 11-fold increased hazard of hepatoblastoma.

• HR for ventricular septal defect-hepatoblastoma: 11.2 (95% CI, 5.9–21.1)
• Ventricular septal defect is one of the most common forms of congenital heart disease
• Hepatoblastoma is a rare pediatric liver cancer
• The association exceeded a 5-fold increase in hazard, meeting the threshold highlighted by the authors as notable

Conotruncal defects were associated with more than 6-fold increased hazard of neuroblastoma.

• HR for conotruncal defects-neuroblastoma: 6.4 (95% CI, 1.9–22.2)
• Conotruncal defects represent a category of structural heart defects affecting the outflow tracts
• Neuroblastoma is a cancer of the sympathetic nervous system commonly diagnosed in young children
• The wide confidence interval reflects smaller numbers of co-occurring cases

The cumulative incidence of cancer was less than 1% for all CHD groups evaluated, indicating that absolute cancer risk in children with nonsyndromic CHD remains low.

• Cumulative incidence of cancer was <1% for all CHD groups evaluated
• The study included 74,755 children with CHD identified from a cohort of approximately 11 million children
• Only nonsyndromic CHD was evaluated, excluding children with known chromosomal or genetic syndromes
• Despite low absolute risk, relative hazards for specific lesion-cancer combinations were substantially elevated

The study evaluated 60 cardiac lesions organized into 7 categories using a large multi-state population-based cohort.

• Data came from Massachusetts, North Carolina, Oklahoma, and Texas
• The total cohort comprised approximately 11 million children
• Cox proportional hazards regression estimated HRs and 95% CIs for cancer in children with each lesion relative to children without congenital anomalies
• Analysis was conducted only when there were ≥3 co-occurring cases of a given lesion-cancer combination
• This represents one of the most detailed assessments of CHD heterogeneity in relation to childhood cancer risk to date

The authors conclude that their findings may assist in generating hypotheses about the causes of cancer in children with congenital heart disease.

• Prior epidemiologic studies had not fully accounted for the pathogenetic and clinical heterogeneity of CHD
• The specificity of associations (e.g., particular lesions linked to particular cancers) suggests potential shared developmental or molecular pathways
• The study was designed to inform both pathogenetic research and clinical management of children with CHD
• The authors note the study's population-based design as a strength for estimating cancer risk