Heart Defect-Cancer Link Present Already in Youth

The association between congenital heart disease (CHD) and cancer is observed in young people too — and it’s not just from radiation exposure, researchers found.

People with CHD included in a Swedish registry showed more than double the risk of cancer compared with healthy controls when followed up to age 41 (1.9% vs 0.9%, HR 2.24, 95% CI 2.01-2.48), according to a report published online in JAMA Network Open.

“This finding suggests that particular attention should be paid to early warning signs of cancer and promotion of a healthy lifestyle,” said the investigators led by Zacharias Mandalenakis, MD, PhD, of the University of Gothenburg, Sweden.

Importantly, cancer risk was elevated whether patients got surgery for their CHD (HR 1.95, 95% CI 1.58-2.33) or not (HR 2.43, 95% CI 2.12-2.76).

“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,” Mandalenakis’ team said. “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.”

Young people with CHD were at particularly high risk of developing malignant neoplasms of the digestive system (RR 3.58, 95% CI 2.58-4.98) but not melanoma and other skin cancers.

The researchers had identified 21,982 people with CHD in Swedish administrative records and matched them 1:10 to healthy controls.

CHD patients with simple and complex heart lesions alike had an excess risk of cancer, as did people across sex and birth cohort subgroups:

• Born in 1970-1979: 2.8% vs 1.5% (HR 2.01, 95% CI 1.73-2.33)
• Born in 1980-1989: 1.6% vs 0.8% (HR 2.21, 95% CI 1.84-2.64)
• Born in 1990-1993: 1.4% vs 0.4% (HR 3.37, 95% CI 2.60-4.35)
• Men: 1.9% vs 0.9% (HR 2.41, 95% CI 2.08-2.79)
• Women: 2.0% vs 1.0% (HR 2.08, 95% CI 1.80-2.41)

That the most recent birth cohort had what appears to be a higher risk may reflect a change in the incidence of cancer, an increase in survival, or both, Mandalenakis and colleagues suggested. “Among patients born from 1970 to 1979, a significant proportion of patients with complex CHD may not have survived long enough to develop cancer.”

“We also found no significant increase in benign tumors among patients with CHD compared with controls, indicating that the overreporting and increased awareness associated with more frequent medical contact is not a likely explanation for our findings,” the authors added.

Nevertheless, their study was based on administrative data where some important clinical information was missing.

“For example, 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,” according to an invited commentary by Michelle Gurvitz, MD, of Boston Children’s Hospital.

Yet this study is consistent with others also based on administrative data in finding an increased prevalence of cancer among people with CHD, she said.

It’s time to “explore the underpinnings of the connection between CHD and cancer,” she urged. “Our understanding of how genetics and environmental exposures may influence the association between CHD and cancer is still in the early stages.”

And even if the causal mechanisms are identified, it will be important to understand the timing and cost-effectiveness of screening strategies, Gurvitz 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,” the editorialist warned.