International trends in the incidence of brain tumours in children and young-adults and their association with indicators of economic development

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Introduction

Brain and central nervous system (CNS) tumours are the second most common type of cancer and the leading cause of cancer-related deaths in children and young-adults [ 1 ]. Approximately one-eighth of brain/CNS cancers occur in 0–24 year-olds and are collectively named childhood brain tumours (CBTs). The World Health Organisation (WHO) classifies tumours using histological, molecular and pathological parameters, and grades them on severity [ 2 ]. Tumours are identified with neuroimaging technology; MRI/CT-scans, and treated with resection surgery, radiotherapy and/or chemotherapy [ 3 ]. Medical advances have improved outcomes; survival ranges from <5% for glioblastomas to >95% for low-grade gliomas, and is often accompanied with increased risk of subsequent neoplasms [ 456 ].

CBT’s aetiology remains poorly understood, although the heterogenous nature suggests complex interactions between biological and environmental factors. Increased CBT risk has been linked to genetic variants; Neurofibromatosis (NF1/2) and Tuberous Sclerosis (TSC1/2), European ancestry, congenital abnormalities and high foetal growth [ 7 ]. Robust evidence exists demonstrating a causal relationship between CBTs and ionising radiation: CT-scans and radiotherapy [ 7 ]. Environmental exposures, such as N-nitroso compounds (NOCs), pesticides, petrochemical/diesel-exhausts, farm-life and infectious agents may alter tumour susceptibility. However, no association has been found between CBTs and non-ionising radiation, including mobile phones [ 7 ].

Three studies have recently analysed WHO’s Cancer Incidence in Five Continents (CI5) database [ 8 ]. Authors found geographical disparities in brain/CNS tumour incidence between countries and significant changes over time between 1993 and 2007 [ 3 , 9 , 10 ]. Further national analyses reported similar findings, where affluent populations were disproportionately impacted, possibly attributable to genetic and/or environmental factors [ 1 , 11 , 12 ]. However, along with ecological fallacy, studies may be influenced by case-ascertainment bias [ 13 ]. Findings might be confounded by differing clinical and reporting practices between countries and time-periods [ 9 ]. The relationships between CBT incidence and Gross Domestic Product (GDP) per capita and Gini index, as indicators of wealth and wealth inequality respectively, remain unknown [ 14 , 15 ]. It is unclear whether findings from adult studies would translate to children, as CBTs show distinctly different distribution patterns to adult tumours. Younger populations must therefore be explored specifically [ 4 ].

This study explored CBT epidemiology in young people aged 0–24 years. Our aims were; 1) to describe international geographical patterns of CBT incidence and trends over time; 2) to investigate the relationship between CBT incidence and economic development, uniquely using GDP per capita and Gini index. Understanding disease spread will support generating aetiological hypotheses to help improve health and reduce inequalities.