Study Finds Neurocutaneous Syndromes Increase Childhood Cancer Risk

Neurocutaneous syndromes—which are already linked to cancer predisposition and sometimes perinatal factors—were found to be associated with increased risk of childhood cancer, especially central nervous system (CNS) tumors, according to a study published in JAMA Network Open.

The study included more than 4.1 million children aged 20 years and younger from 1973 to 2015, whose data—including that of both biological parents—were pulled from the Swedish National Medical Birth Register (MBR) and analyzed between April 2021 and May 2023.

Slightly more than half of the children were male (51.4%), with a median (IQR) follow-up of 20 (9.7-20) years. Using the MBR, the authors identified 2791 children with any diagnosed neurocutaneous syndrome. Of these 2791 children, 1783 had neurofibromatosis type 1 (NF1), 444 had tuberous sclerosis (TSC), 63 had von Hippel-Lindau disease, and 39 had ataxia-telangiectasia.

Compared with the general population, having any neurocutaneous syndrome was linked to an increased pediatric cancer risk (HR, 34.9; 95% CI, 30.8-39.6), with the risk particularly pronounced for CNS tumors (HR, 111.7; 95% CI, 96.8-128.8). For children with TSC, the risk of CNS tumors was more pronounced (adjusted HR [aHR], 99.4; 95% CI, 69.8-141.7), and the authors observed similarly increased risks for malignant CNS tumors.

Additionally, the aHR for all pediatric cancers varied from 22.4 (95% CI, 8.4-59.7) among children with von Hippel-Lindau disease to 31.3 (95% CI, 26.5-36.9) for children with NF1.

“Although previous cohort studies on NF1 and cancer risk reported lesser associations than what we have observed in our study, they did not focus on pediatric cancer, but instead investigated cancer risk at any age and in individuals younger than 50 years,” the authors noted. “To date, only 1 Finnish study has evaluated the risk of pediatric cancer among children with NF1, with findings similar to ours.”

For children with ataxia-telangiectasia, the increased risk was associated with lymphomas instead (HR, 233.1; 95% CI, 75.0-724.1). However, it’s important to note that this is based on only 3 cases of lymphoma among this subgroup. Additionally, the risk of leukemia only increased for children with NF1 (HR, 4.1; 95% CI, 1.7-9.8).

According to the authors, there were several perinatal factors—high birth weight, being born large for gestational age, preterm birth, low 5-minute Apgar score, and large head circumference—that had lesser associations with pediatric cancer, though the associations still exist and have been known prior to this study. These associations did not change after adjusting for neurocutaneous syndromes.

“Therefore, other biological mechanisms likely underlie any association between specific perinatal factors and childhood cancer,” the authors said. “Our findings underscore the importance of the recently published cancer screening recommendations in children with NF1
and TSC.”

Reference

Kampitsi CE, Nordgren A, Mogensen H, Pontén E, Feychting M, Tettamanti G. Neurocutaneous syndromes, perinatal factors, and the risk of childhood cancer in Sweden. JAMA Netw Open. 2023;6(7):e2325482. Published 2023 Jul 3. doi:10.1001/jamanetworkopen.2023.25482