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

Abstract

Epidemiological studies have shown an increased prevalence of cancer in patients with congenital heart disease (CHD) as compared with the general population. The underlying risk factors for the acquired cancer risk remain poorly understood, and shared genetic anomalies and cumulative radiation exposure from repeated imaging and catheterization procedures may be contributing factors. In the present review, we provide an update on the most recent literature regarding the associations between CHD and cancer, with a particular focus on genetic etiology and radiation exposure from medical procedures. The current evidence indicates that children with CHD may be a high-risk population, already having the first genetic "hit", and, consequently, may have increased sensitivity to ionizing radiation from birth or earlier. Future research strategies integrating biological and molecular measures are also discussed in this article.

Keywords: cancer; congenital heart disease; genetics; ionizing radiation.

Figure 1

Molecular epidemiology may overcome some major limitations of traditional epidemiology and provide insights into disease causation. Validated biomarkers of effects can help to delineate the continuum of events between exposure and resulting cancer by identifying early changes in the natural history of cancer process.

Figure 2

Illustration of unifying model for understanding the relationship between CHD, radiation exposure, and cancer. This model supports the notion that germline variations in CHD increase the susceptibility of induced DNA mutations.