Identifying the Causes of Brain Tumors

Kyle Walsh, PhD, is associate professor and director of the Division of Neuro-Epidemiology in the Department of Neurosurgery at Duke. He is a population scientist investigating the genetic and environmental causes of cancer in children and adults, with a particular emphasis on central nervous system malignancies. Here, he answers questions about the epidemiology of brain tumors.

How common are brain tumors?

Primary brain tumors account for about 1% of new cancer cases and about 2% of cancer deaths in the United States. These tumors are very heterogeneous, and there more than 100 different subtypes which vary in frequency by age, sex, and race/ethnicity.

Has there been an increase in the number of brain tumors in recent years?

Time trend studies report a modest increase in brain tumor incidence over the past three decades, but this could be the result of improved reporting and increased use of diagnostic imaging.

Who gets brain tumors?

With respect to glioma, adults are affected far more frequently than children; whites more than African Americans; and males more than females. Conversely, rates of meningioma and pituitary tumors are higher in women and in African Americans. 

What external risk factors for brain tumors have been studied?

Epidemiologic studies have explored numerous exogenous factors for association with central nervous system tumor development. Among the best validated is ionizing radiation, which increases risk. Years ago, head irradiation was used to treat ringworm of the scalp. Today, it is recognized as a causative factor for meningioma. Another well documented factor is a history of chickenpox, which decreases glioma and meningioma risk.

What about dental X-rays and the use of mobile phones?

Studies have shown that low-dose radiation from dental films taken on an annual basis is associated with an increased risk of meningioma. (Claus et al 2012) 

Current evidence does not support an association between mobile phone use and brain tumor risk. Other factors that probably do not increase the risk of central nervous system (CNS) tumors are diagnostic radiation, head injury, residential power lines, cigarette smoking, and alcohol consumption. 

What about endogenous factors?

Validated endogenous factors include longer telomere length (which increases risk) and a history of atopic allergies like hay fever, allergic asthma and eczema (which decreases risk). 

Additionally, genetic studies have identified 33 common inherited variants that confer risk of central nervous system tumors (28 for glioma, 2 for meningioma, 3 for pituitary adenoma). The vast majority of glioma is sporadic, but 5% of cases may be attributable to an underlying inherited gene mutation. (Bainbridge et al 2014)

How much research has there been on the causes of pediatric brain tumors?

Additional studies are under way for pediatric CNS tumor predisposition, but such studies have historically had limited sample size. Although the identification of risk factors for CNS tumors is challenging, multi-institutional collaborations can enable rapid progress. Additionally, the incorporation of molecularly-stratified tumor subgroups into etiologic research will increase precision in estimating risk and may identify new modifiable risk factors. Two recent studies of childhood ependymoma (a form of glioma) identified increased risk associated with longer telomere length and with European ancestry, both of which have previously been confirmed to increase risk of the more common adult gliomas. (Zhang, et al. 2020)

 

About the Walsh Lab at Duke

Kyle Walsh’s lab uses data generated by genome-wide SNP arrays, genome-wide methylation arrays, and whole-exome sequencing to identify both heritable and modifiable causes of cancer. Research in the Walsh Lab is collaborative, using a combination of population science and functional genomics approaches to explore how genetic risk factors interact with the somatic genome, the epigenome, and the environment to impact cancer risk. 

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