Cancer incidence among children and young adults with congenital heart disease

By Dr. Ananya Mandal, MDJul 7 2019

Researchers led by Zacharias Mandalenakis from University of Gothenburg in Gothenburg, Sweden, have looked at data from the National registry in Sweden to assess the risk of cancers among children and young adults who have been diagnosed with congenital heart disease compared to those who did not have such a diagnosis. Their results showed that these children often are at a double risk of cancer.

The results of the study titled, “Risk of Cancer Among Children and Young Adults With Congenital Heart Disease Compared With Healthy Controls,” were published in the latest issue of the journal JAMA Network Open in the Cardiology section.

The team explored the hypothesis that children and young adults (birth to 41 years of age) who had been diagnosed with congenital heart disease were at a greater risk of getting cancers. They looked at national registry data from 21,982 children and young adults who had been diagnosed with congenital heart disease and compared them with 219,816 age and gender matched controls with no such disease. The risk of cancers among these children was found to be two fold higher compared to controls wrote the researchers. They add that all children and young adults with congenital heart disease thus should be screened for cancers systematically.

Congenital heart disease : Tetralogy of Fallot. Image Credit: Alila Medical Media / Shutterstock

The registry - Patient and Cause of Death Registers, contained persons diagnosed with congenital heart disease born from 1970 to 1979, 1980 to 1989, and 1990 to 1993. For each of these cases 10 healthy controls of same sex, age and living in the same county were chosen to fortify the results. All health data of the participants were gathered between 1970 until 2011. Thereafter the team analyzed this large amount of data taking around six months (between September 2018 and February 2019). Each of the participant’s social security number was coded so that their anonymity was maintained, write the researchers.

The results from the registry revealed that 2 percent of those with congenital heart disease (428 persons) and 0.9 percent of those without (healthy controls 2,072 persons) developed cancer during the study period. Further the average age of those with congenital heart disease being diagnosed with cancers was around 26.6 years and 51.6 percent of them were males. Average age at cancer detection was 28.5 years among the controls and similarly around half (51.6 percent) were men.

Overall one in 50 among those with congenital heart disease developed cancer by the age of 41 years and the risk seemed to rise with the later birth cohorts. For example the risk of cancers among those with congenital heart disease born between 1990 and 1993 was higher than those born before. Those with a complex heart condition (such as conotruncal defects write the authors) had a greater risk of cancers than controls.

The authors add that this was the first such study that looked at “long-term incidence of cancer from birth to a maximum age of 41 years among patients with all types of CHD (congenital heart disease), with or without surgery.” The team noted that the increased risk of cancer among those with this condition was high at birth and rose with each 10 year birth cohort. They write, “1.5% of patients with CHD in the cohort who were born from 1990 to 1993 had developed cancer by age 18 years or younger.” They explain that those born in the seventies probably did not live long enough to get cancers as the present surgical approaches to congenital heart disease were not so developed. That could one of the reasons for the rise in cancer incidences among those born later in the registry, they add.

The team explained that those with congenital heart disease tend to have “lower isotonic muscle function, reduced oxygen uptake, and higher exercise intolerance,” compared to controls. This could mean more physical inactivity and thus raise the risk of getting cancers, the authors speculate. Further, cancers of the digestive system were found to be more common among those with congenital heart disease compared to healthy controls they wrote (a ratio of 3.58 compared to other forms of cancers).

The team said in a statement, “This finding suggests that particular attention should be paid to early warning signs of cancer and promotion of a healthy lifestyle.” They add, “Our study findings add to the ongoing discussion on whether there is an association of the use of cardiac procedures with the risk of malignancy, potentially mediated by exposure to low-dose ionizing radiation. Our data would support that the increased risk of cancer in children and young adults with CHD is not a simple function of radiation exposure.”

Authors concluded, “Children and young adult patients with CHD had an increased risk of developing cancer compared with healthy matched controls, and the risk was significantly higher among patients with CHD from the most recent birth cohort. An increased risk of cancer in all CHD lesion groups was found, and a systematic screening for cancer could be considered for this at-risk group of patients.” The team wrote that other factors that influence cancer incidence among this group such as radiation exposure, use of antibiotics and lessening of biological stress should be explored in order to understand this association.

In an accompanying editorial Michelle Gurvitz, MD, of Boston Children's Hospital, wrote about the gap in knowledge saying, “...information regarding lifestyle-related factors, such as primary or secondary smoking exposure, family medical history, dietary habits, and physical activity, is critically important to understanding cancer epidemiology among patients with CHD and is not available in administrative records.” She added that it was time to, “explore the underpinnings of the connection between CHD and cancer” and said, “Our understanding of how genetics and environmental exposures may influence the association between CHD and cancer is still in the early stages.” She explained that cost effectiveness of screening strategies need to be understood to optimize results. She said, “Because the population with CHD is large and diverse, with different patterns of care, interventions, exposures, and genetic predispositions, it is essential to develop more-specific information before drawing conclusions and implementing care strategies regarding cancer risk.”