Risk of cancer in young and older patients with congenital heart disease and the excess risk of cancer by syndromes, organ transplantation and cardiac surgery: Swedish health registry study (1930-2017)


Risk of cancer in young and older patients with congenital heart disease and the excess risk of cancer by syndromes, organ transplantation and cardiac surgery: Swedish health registry study (1930-2017)

Christina Karazisi, Mikael Dellborg, Karin Mellgren, Kok Wai Giang, Kristofer Skoglund, Peter Eriksson, Zacharias Mandalenakis. Lancet Reg Health Eur. 2022 May 29;18:100407. doi: 10.1016/j.lanepe.2022.100407. eCollection 2022 Jul. PMID: 35663362


Take-Home Points:

1) There is a 23% increased risk of cancer in young and older patients with congenital heart disease when compared to matched controls without congenital heart disease

2) The risk is higher in children and those who were born in later birth cohorts

3) The risk remains elevated after excluding patients with genetic syndromes and transplant recipients

Overall Congenital cardiac surgery was not associated with an increased risk of cancer except in children who underwent cardiac surgery during the first year of life




Commentary from Dr. Venu Amula (Salt Lake City, UT, USA), section editor of Pediatric & Fetal Cardiology

Karazasi et al. performed an observational case-control study using the Swedish health registry to investigate the risk of cancer in young and older patients with CHD and to evaluate the excess risk of cancer by syndromes, organ transplantation, and cardiac surgery. With the increasing survival of patients with congenital heart disease, they are at risk of acquired cardiovascular conditions and other diseases such as cancer. However, limited studies exist quantifying such a risk in patients with congenital heart disease compared to the general population.

The authors of this study used data from the Swedish National Inpatient Register, the Swedish National Outpatient Register, and the Swedish Cause of Death Register. Inclusion criteria included patients born between 1930 and 2017 with a diagnosis of CHD. ICD codes were used for diagnosis. Each patient with CHD was matched by sex and birth year with ten controls without CHD from the general population, identified from the Swedish Total Population Register. Follow-up times for CHD and control populations were estimated from birth until the event (cancer), death, or the end of the study period (31 December 2017), whichever occurred first. Incidence rates were reported as per 10,000 person-years and were estimated as the number of events divided by the total follow-up time of the population. Incidence rate ratio (IRR) was defined as the relative difference between CHD and the control population, with 95% confidence intervals (CI) Cox proportional hazard regression models used to obtain hazard ratios (HR) with 95% CIs. For all models, the control population was considered the reference population.

The authors identified 89,542 patients born between 1930 and 2017 who were registered with the diagnosis of CHD and 890,472 controls who were matched by birth year and sex. As noted in the table below, the baseline characteristics were similar in cases and controls. After a median follow-up time of 58.8 years for CHD patients and 61.3 years for controls, 4.5% of patients with CHD and 4.0% of the control population developed cancer. The cancer risk was 23% more in patients with CHD than in controls. The increased risk was maintained after excluding patients with syndromes and organ transplant recipients. When studying the cumulative incidence of cancer according to the birth cohort, the incidence of cancer was significantly higher in the CHD population from the youngest birth cohorts.

Figure:   Cumulative incidence of cancer risk by birth cohort: Birth cohorts 1970−1989 and 1990-2017.


This study is of utmost importance and raises several important questions. The reasons for such an increased cancer risk remain elusive, but several are plausible. Genetic predisposition, increased exposure to low ionizing radiation as a part of diagnostic and therapeutic procedures, and early thymectomy with immune dysregulation are possible explanations without any direct evidence incriminating them. The association of higher cancer risk with younger birth cohorts does follow the increased surgical and catheter-based intervention trends in recent periods. Longitudinal studies involving large populations may provide more insight, but in the meanwhile, cardiologists should be aware of this higher risk and engage in heightened surveillance of young patients.