Dissertation: Congenital heart disease, genetic syndromes, and childhood cancer

What is the thesis about?
The primary focus of the thesis is on deepening the comprehension of childhood cancer etiology and survival, by using high-quality nationwide Nordic administrative and healthcare register data. 

The potential risk factors we investigated were certain congenital conditions, namely congenital heart disease (CHD) and neurocutaneous syndromes, as well as certain perinatal characteristics. Additionally, we investigated survival outcomes of childhood cancer in relation to CHD. Finally, we explored the influence of parental occupational exposures on the risk of de novo neurocutaneous syndromes in the offspring.

Can you tell us about some interesting results?
In the studies included in this thesis, we found that CHD is linked to both an increased risk of childhood cancer (particularly for lymphomas and hepatoblastomas) and an increased mortality post-childhood cancer diagnosis (primarily for lymphomas). 

This thesis also highlights neurocutaneous syndromes as risk factors for childhood cancer. The most common neurocutaneous syndromes, neurofibromatosis type 1 and tuberous sclerosis complex, showed a particularly noteworthy increase in childhood cancer risk, especially for tumors of the central nervous system. Furthermore, we identified weak associations between several perinatal characteristics and childhood cancer, independent of neurocutaneous syndromes. These characteristics include high birth weight, preterm birth, low 5-minute Apgar score, large head circumference, and being large for gestational age. 

Lastly, we delved into the impact of parental occupational exposures on the risk of de novo cancer-linked neurocutaneous syndromes. Exposure to various chemical agents in the workplace emerged as a potential risk factor for de novo neurofibromatosis type 1 in the offspring. Notably, stronger associations were observed for maternal exposures.

What further research is needed in the area?
Gaining a comprehensive understanding of the mechanisms underlying our findings necessitates further inquiry. For instance, it remains to be explored whether shared mutations or radiation exposure from cardiac procedures contribute to the heightened risk of lymphoma in children with CHD. Additionally, the lower survival rates for lymphoma among children with CHD prompt questions regarding the potential limitations posed by treatment-related cardiac complications on the utilization of highly effective cancer treatments.

About the dissertation

Time: 26 January, 9.00 a.m.
Location: Petrénsalen, Nobels väg 12 B, Karolinska institutet

Principal Supervisor
Giorgio Tettamanti, Associate Professor, Institute of Environmental Medicine, KI

Opponent
Quinn Ostrom, Assistant Professor, Duke University School of Medicine 

On January 25 at 13:00-14:00 Quinn Ostrom will give a lecture Using Population-Based Data for Surveillance and Discovery in Primary Brain Tumors in the United States