Abstract
Pediatric central nervous system tumors (pCNSTs) are the second most common malignancy among children less than 20 years of age and the most common solid tumor of childhood. The incidence of these tumors has been steadily increasing over the past decades. The etiology as well as the mechanism of the development of a majority of pCNSTs remains elusive. Although numerous genetic and epigenetic changes have been identified with both development and outcome of pCNSTs, most of these alterations do not define a majority of tumors. Though ionizing radiation is a risk factor for pCNST development, evidence for the role of other environmental factors such as pesticides,
N-nitroso compounds, and viral infections remain debatable. It is probable that the etiology of pediatric brain tumors, as is the case with most cancers, is multifactorial. Interaction of environmental factors with genetic and epigenetic changes may be responsible for the development of the particular type of pCNST in an individual. The assessment of gene–environment interaction in pCNSTs has been more complex because of the lack of sound molecular epidemiological studies with a more complete picture of individual cancer risk associated with environmental exposure and genetic analysis. The increased susceptibility of the developing fetus and child to environmental insults should also be considered as a part in the development of pCNSTs. This review describes the chromosomal, genetic, and epigenetic changes found in common pCNSTs, and summarizes the alterations found in pCNSTs that may influence mitochondrial–nuclear signaling and the basis for interaction between environment and genetic factors.