Risk factors for childhood and adult primary brain tumors

Abstract

Primary brain tumors account for ~1% of new cancer cases and ~2% of cancer deaths in the United States; however, they are the most commonly occurring solid tumors in children. These tumors are very heterogeneous and can be broadly classified into malignant and benign (or non-malignant), and specific histologies vary in frequency by age, sex, and race/ethnicity. Epidemiological studies have explored numerous potential risk factors, and thus far the only validated associations for brain tumors are ionizing radiation (which increases risk in both adults and children) and history of allergies (which decreases risk in adults). Studies of genetic risk factors have identified 32 germline variants associated with increased risk for these tumors in adults (25 in glioma, 2 in meningioma, 3 in pituitary adenoma, and 2 in primary CNS lymphoma), and further studies are currently under way for other histologic subtypes, as well as for various childhood brain tumors. While identifying risk factors for these tumors is difficult due to their rarity, many existing datasets can be leveraged for future discoveries in multi-institutional collaborations. Many institutions are continuing to develop large clinical databases including pre-diagnostic risk factor data, and developments in molecular characterization of tumor subtypes continue to allow for investigation of more refined phenotypes. Key Point 1. Brain tumors are a heterogeneous group of tumors that vary significantly in incidence by age, sex, and race/ethnicity.2. The only well-validated risk factors for brain tumors are ionizing radiation (which increases risk in adults and children) and history of allergies (which decreases risk).3. Genome-wide association studies have identified 32 histology-specific inherited genetic variants associated with increased risk of these tumors.

Sex-specific aspects of epidemiology, molecular genetics and outcome: primary brain tumours

“…Only two non-genetic risk factors have been reported in primary brain tumours: ionising radiation (which increases the risk) and medical history of allergies (which decreases the risk). 9 There are only a few explanations supporting a difference between incidence in females and males. In a first Genome-Wide Association Study (GWAS), a significant association between a diagnosis of all glioma and glioblastoma and one single nucleotide polymorphism (SNP) (rs11979158) at 7p11.22 locus, near epidermal growth factor receptor (EGFR) in males only and an association between all glioma and glioblastoma and a large region on 3p21.31 was noted for females only supporting a potential sex-specific risks (Ostrom 2018).…”

A Weighted Genetic Risk Score of Adult Glioma Susceptibility Loci Associated with Pediatric Brain Tumor Risk

“…In addition, this line of research provides the basis to develop comprehensive risk prediction models including both genetic and environmental factors for brain tumors that eventually may lead to brain tumor prediction and prevention. This can be achieved by incorporating large collaborative genetic association studies and high quality registration data and could be leveraged by refinement of molecular classification and development of somatic characteristics of brain tumors 10 .…”

Pre-diagnostic Circulating Concentrations of Fat-soluble Vitamins and Risk of Glioma in Three Cohort Studies

“…Gliomas are the most common malignant brain tumors in adults and arise from glial tissue. 1 Patients with these tumors generally have poor prognoses and survival rates. 2 In particular, glioblastoma (GBM), which accounts for more than half of all gliomas (~60%), has a 5-year relative survival of approximately 7%.…”