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.

Keywords: epidemiology; glioma; meningioma; pediatric brain tumors; risk factors.

Fig. 1

ORs, 95% CIs, and P-values for previously identified glioma risk SNPs by molecular subtype (data from Labreche et al).

Fig. 2

Average annual incidence of primary brain and CNS tumors in the United States by age and (a) behavior, (b) selected malignant histologies, and (c) selected non-malignant histologies, and average annual age-adjusted incidence by behavior and (d) sex and (e) race/ethnicity (Central Brain Tumors Registry of the United States [CBTRUS], 2011–2015).

Fig. 3

ORs and 95% CIs selected potential risk factors for primary brain tumors for glioma, meningioma, vestibular schwannoma, and pituitary tumors (See Supplementary Note 3 for data sources).