The relationship between congenital heart disease and cancer in Swedish children: A population-based cohort study

Abstract

Background Birth defects have been consistently associated with elevated childhood cancer risks; however, the relationship between congenital heart disease (CHD) and childhood cancer remains conflicting. Considering the increasing patient population with CHD after improvements in their life expectancies, insights into this relationship are particularly compelling. Thus, we aimed to determine the relationship between CHD and cancer in Swedish children. Methods and findings All individuals registered in the Swedish Medical Birth Register (MBR) between 1973 and 2014 were included in this population–based cohort study (n = 4,178,722). Individuals with CHD (n = 66,892) were identified from the MBR and National Patient Register, whereas cancer diagnoses were retrieved from the Swedish Cancer Register. The relationship between CHD and childhood cancer (<20 years at diagnosis) was evaluated using Cox proportional hazards regression models. We observed increased risks of cancer overall, leukemia, lymphoma, and hepatoblastoma in children with CHD, but after adjustment for Down syndrome, only the increased lymphoma (hazard ratio (HR) = 1.64, 95% confidence interval (CI) 1.11 to 2.44) and hepatoblastoma (HR = 3.94, 95% CI 1.83 to 8.47) risk remained. However, when restricting to CHD diagnoses from the MBR only, i.e., those diagnosed around birth, the risk for childhood cancer overall (HR = 1.45, 95% CI 1.23 to 1.71) and leukemia (HR = 1.41, 95% CI 1.08 to 1.84) was more pronounced, even after controlling for Down syndrome. Finally, a substantially elevated lymphoma risk (HR = 8.13, 95% CI 4.06 to 16.30) was observed in children with complex CHD. Limitations of the study include the National Patient Register not being nationwide until 1987, in addition to the rareness of the conditions under study providing limited power for analyses on the rarer cancer subtypes. Conclusions We found associations between CHD and childhood lymphomas and hepatoblastomas not explained by a diagnosis of Down syndrome. Stronger associations were observed in complex CHD.

Role of non‐chromosomal birth defects on the risk of developing childhood Hodgkin lymphoma: A Children's Oncology Group study

“…Subtype missing 3 (0.6) 1 (4.5) 0 (0.0) 2 (0.5) study of CHDs, after adjustment for Down syndrome, CHD was associated with increased risk of lymphoma (HR: 1.6; 95% CI: 1.1-2.4; n = 1,273). In this cohort, an elevated risk of lymphoma (HR = 8.13, 95% CI: 4.06-16.30) was also observed in children with complex CHD, 58 as previously reported. 59,60 While this was not observed in our study, it could be due to the limited number of cases (n = 4) and controls (n = 7)…”

Thymic Atrophy and Immune Dysregulation in Infants with Complex Congenital Heart Disease

“…In this study, we analyzed the impact of the cardiac defect on T-cell development in patients with CHD, a population known to be at increased risk for infections, cancer, and autoimmune diseases [ 16 , 46 – 49 ]. Previous research has mainly linked the compromised T-cell compartment observed in these patients with early-life thymectomy [ 50 – 52 ].…”

Congenital Heart Disease and the Risk of Cancer: An Update on the Genetic Etiology, Radiation Exposure Damage, and Future Research Strategies

“…Recently, a large population-based cohort study by Kampitsi et al [ 10 ] reported a 64% increased risk of lymphoma and more than 300% of hepatoblastoma, respectively. The risk of lymphoma was particularly elevated in children with complex CHD and that of leukemia in patients with Down syndrome [ 10 ]. Additionally, a recent Swedish register-based study confirmed the increased cancer risk in patients with CHD [ 15 ].…”

“…Children with congenital defects have a significantly higher risk of developing some type of cancer, including leukemia, tumors of the central nervous system, tumors of the sympathetic nervous system, and soft tissue sarcomas [ 3 , 4 , 5 , 6 , 7 , 8 ]. Cancer risk is especially increased in CHD children with complex defects [ 9 , 10 ].…”