Abstract
BACKGROUND: Individuals with genetic syndromes can manifest both congenital heart disease (CHD) and cancer attributable to possible common underlying pathways. To date, reliable risk estimates of hematopoietic cancer (HC) among children with CHD based on large population-based data remain scant. This study sought to quantify the risk of HC by the presence of genetic syndrome among children with CHD. METHODS AND RESULTS: Data sources were the Canadian CHD database, a nationwide database on CHD (1999-2017), and the CCR (Canadian Cancer Registry). Standardized incidence ratios were calculated for comparing HC incidences in children with CHD with the general pediatric population. A modified Kaplan-Meier curve was used to estimate the cumulative incidence of HC with death as a competing risk. A total of 143 794 children (aged 0-17 years) with CHD were followed up from birth to age 18 years for 1 314 603 person-years. Of them, 8.6% had genetic syndromes, and 898 HC cases were observed. Children with known syndromes had a substantially higher risk of incident HC than the general pediatric population (standardized incidence ratio, 13.4 [95% CI, 11.7-15.1]). The cumulative incidence of HC was 2.44% (95% CI, 2.11-2.76) among children with a syndrome and 0.79% (95% CI, 0.72-0.87) among children without a syndrome. Acute myeloid leukemia had a higher cumulative incidence during early childhood than acute lymphoblastic leukemia. CONCLUSIONS: This is the first large population-based analysis documenting that known genetic syndromes in children with CHD are a significant predictor of HC. The finding could be essential in informing risk-stratified policy recommendations for cancer surveillance in children with CHD.